[{"intvolume":"         8","volume":8,"_id":"19963","external_id":{"isi":["001511452100001"],"pmid":["40537284"]},"issue":"9","isi":1,"author":[{"full_name":"Kuhn, Kenneth D","id":"7deed7e0-0133-11f0-8590-c4600b08d0f4","last_name":"Kuhn","first_name":"Kenneth D"},{"full_name":"Cho, Ukrae H.","last_name":"Cho","first_name":"Ukrae H."},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","last_name":"Hetzer","full_name":"Hetzer, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed"}],"ddc":["570"],"publisher":"Embo Press","project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"article_number":"e202503208","year":"2025","pmid":1,"date_published":"2025-09-01T00:00:00Z","article_processing_charge":"Yes","publication_identifier":{"eissn":["2575-1077"]},"date_created":"2025-07-06T22:01:22Z","publication":"Life Science Alliance","abstract":[{"lang":"eng","text":"The acquisition of cellular identity requires large-scale alterations in cellular state. The noncanonical proteasome activator PSME3 is known to regulate diverse cellular processes, but its importance for differentiation remains unclear. Here, we demonstrate that PSME3 binds dynamically to highly active promoters over the course of differentiation. However, loss of PSME3 does not globally affect mRNA transcription. We find instead that PSME3 influences the levels of several adhesion-related proteins and acts upstream of the HSP90 co-chaperone NUDC to regulate cell motility and myoblast differentiation in a proteasome-independent manner. Our findings reveal several new facets of PSME3 functionality and highlight its importance for the differentiation of myogenic cells."}],"date_updated":"2026-05-20T08:38:04Z","DOAJ_listed":"1","type":"journal_article","file_date_updated":"2025-12-30T09:17:09Z","PlanS_conform":"1","OA_type":"gold","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"PSME3 regulates migration and differentiation of myoblasts","OA_place":"publisher","APC_amount":"4215,38 EUR","article_type":"original","oa":1,"has_accepted_license":"1","file":[{"file_size":5471288,"creator":"dernst","date_updated":"2025-12-30T09:17:09Z","file_name":"2025_LifeScienceAlliance_Kuhn.pdf","date_created":"2025-12-30T09:17:09Z","file_id":"20904","relation":"main_file","checksum":"591d47aa39fc969986c7d3b966890f5f","content_type":"application/pdf","success":1,"access_level":"open_access"}],"citation":{"chicago":"Kuhn, Kenneth D, Ukrae H. Cho, and Martin Hetzer. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>. Embo Press, 2025. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>.","mla":"Kuhn, Kenneth D., et al. “PSME3 Regulates Migration and Differentiation of Myoblasts.” <i>Life Science Alliance</i>, vol. 8, no. 9, e202503208, Embo Press, 2025, doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>.","short":"K.D. Kuhn, U.H. Cho, M. Hetzer, Life Science Alliance 8 (2025).","ista":"Kuhn KD, Cho UH, Hetzer M. 2025. PSME3 regulates migration and differentiation of myoblasts. Life Science Alliance. 8(9), e202503208.","ieee":"K. D. Kuhn, U. H. Cho, and M. Hetzer, “PSME3 regulates migration and differentiation of myoblasts,” <i>Life Science Alliance</i>, vol. 8, no. 9. Embo Press, 2025.","ama":"Kuhn KD, Cho UH, Hetzer M. PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. 2025;8(9). doi:<a href=\"https://doi.org/10.26508/lsa.202503208\">10.26508/lsa.202503208</a>","apa":"Kuhn, K. D., Cho, U. H., &#38; Hetzer, M. (2025). PSME3 regulates migration and differentiation of myoblasts. <i>Life Science Alliance</i>. Embo Press. <a href=\"https://doi.org/10.26508/lsa.202503208\">https://doi.org/10.26508/lsa.202503208</a>"},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"status":"public","scopus_import":"1","acknowledgement":"All proteomics analysis was done by the ISTA LSF Mass Spectrometry Service: Ewelina Dutkiewicz-Kopczynska processed the samples (digest and cleanup); Bella Bruszel optimized the acquisition methods, acquired the data, and performed all searches; and Armel Nicolas provided pre- and post-project consulting and post-processed the search results using a development version of their data analysis package, proteoCraft (publication pending). The authors would like to thank Saki for their clarity of thought and insight, as well as Dr. Lorenzo Puri and the members of his laboratory for invaluable discussions relating to the project. This research was further supported by the Lab Support Facility and the Imaging and Optics Facility of ISTA.","doi":"10.26508/lsa.202503208","day":"01","publication_status":"published","department":[{"_id":"MaHe"}],"corr_author":"1","month":"09","language":[{"iso":"eng"}],"quality_controlled":"1","oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}]},{"year":"2025","publisher":"Elsevier","ddc":["570"],"article_processing_charge":"Yes (in subscription journal)","page":"645-654","date_published":"2025-09-01T00:00:00Z","pmid":1,"volume":48,"intvolume":"        48","author":[{"full_name":"Hetzer, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"Hetzer","orcid":"0000-0002-2111-992X","first_name":"Martin W"},{"first_name":"Tomohisa","last_name":"Toda","full_name":"Toda, Tomohisa"}],"isi":1,"external_id":{"isi":["001568965400001"],"pmid":["40744775"]},"_id":"20154","issue":"9","scopus_import":"1","acknowledgement":"The work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (470322152 – T1347/3-1; 497658532 – T1347/4-1; 507965872 – T1347/5-1; and 460333672 – CRC1540 Exploring Brain Mechanics) to T.T., the Schram Foundation (T.T.), the European Research Council (ERC-2018-STG, 804468 EAGER; ERC-2023-COG, 101125034 NEUTIME) to T.T., the Hans-Georg Geis und Xue Hong Dong-Geis Foundation and Forschungsstiftung Medizin am Universitätsklinikum Erlangen to T.T., and the Interdisciplinary Centre for Clinical Research Erlangen (Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Erlangen; P162 to T.T.). We thank Dr Laura J. Harrison for editing assistance.","status":"public","citation":{"ista":"Hetzer M, Toda T. 2025. Long-lived cellular molecules in the brain. Trends in Neurosciences. 48(9), 645–654.","mla":"Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the Brain.” <i>Trends in Neurosciences</i>, vol. 48, no. 9, Elsevier, 2025, pp. 645–54, doi:<a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">10.1016/j.tins.2025.07.004</a>.","chicago":"Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the Brain.” <i>Trends in Neurosciences</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">https://doi.org/10.1016/j.tins.2025.07.004</a>.","short":"M. Hetzer, T. Toda, Trends in Neurosciences 48 (2025) 645–654.","ama":"Hetzer M, Toda T. Long-lived cellular molecules in the brain. <i>Trends in Neurosciences</i>. 2025;48(9):645-654. doi:<a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">10.1016/j.tins.2025.07.004</a>","apa":"Hetzer, M., &#38; Toda, T. (2025). Long-lived cellular molecules in the brain. <i>Trends in Neurosciences</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.tins.2025.07.004\">https://doi.org/10.1016/j.tins.2025.07.004</a>","ieee":"M. Hetzer and T. Toda, “Long-lived cellular molecules in the brain,” <i>Trends in Neurosciences</i>, vol. 48, no. 9. Elsevier, pp. 645–654, 2025."},"file":[{"date_created":"2025-12-29T13:47:27Z","file_id":"20873","file_name":"2025_TrendsNeurosciences_Hetzer.pdf","date_updated":"2025-12-29T13:47:27Z","creator":"dernst","file_size":327847,"access_level":"open_access","success":1,"content_type":"application/pdf","checksum":"90942491b499f70b0bf48b8aec2e7387","relation":"main_file"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"quality_controlled":"1","language":[{"iso":"eng"}],"oa_version":"Published Version","month":"09","corr_author":"1","day":"01","doi":"10.1016/j.tins.2025.07.004","department":[{"_id":"MaHe"}],"publication_status":"published","PlanS_conform":"1","file_date_updated":"2025-12-29T13:47:27Z","date_updated":"2025-12-29T13:47:58Z","type":"journal_article","abstract":[{"text":"In long-lived mammals, including humans, brain cell homeostasis is critical for maintaining brain function throughout life. Most neurons are generated during development and must maintain their cellular identity and plasticity to preserve brain function. Although extensive studies indicate the importance of recycling and regenerating cellular molecules to maintain cellular homeostasis, recent evidence has shown that some proteins and RNAs do not turn over for months and even years. We propose that these long-lived cellular molecules may be the basis for maintaining brain function in the long term, but also a potential convergent target of brain aging. We highlight key discoveries and challenges, and propose potential directions to unravel the mystery of brain cell longevity.","lang":"eng"}],"publication_identifier":{"issn":["0166-2236"],"eissn":["1878-108X"]},"date_created":"2025-08-10T22:01:29Z","publication":"Trends in Neurosciences","oa":1,"has_accepted_license":"1","OA_place":"publisher","article_type":"original","OA_type":"hybrid","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Long-lived cellular molecules in the brain"},{"month":"04","corr_author":"1","related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/nerve-cells-old-at-heart/","relation":"press_release"}]},"day":"04","doi":"10.1126/science.adf3481","department":[{"_id":"MaHe"}],"publication_status":"published","oa_version":"Submitted Version","language":[{"iso":"eng"}],"quality_controlled":"1","status":"public","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615865"}],"citation":{"ista":"Zocher S, Mccloskey A, Karasinsky A, Schulte R, Friedrich U, Lesche M, Rund N, Gage FH, Hetzer M, Toda T. 2024. Lifelong persistence of nuclear RNAs in the mouse brain. Science. 384(6691), 53–59.","mla":"Zocher, Sara, et al. “Lifelong Persistence of Nuclear RNAs in the Mouse Brain.” <i>Science</i>, vol. 384, no. 6691, AAAS, 2024, pp. 53–59, doi:<a href=\"https://doi.org/10.1126/science.adf3481\">10.1126/science.adf3481</a>.","chicago":"Zocher, Sara, Asako Mccloskey, Anne Karasinsky, Roberta Schulte, Ulrike Friedrich, Mathias Lesche, Nicole Rund, Fred H. Gage, Martin Hetzer, and Tomohisa Toda. “Lifelong Persistence of Nuclear RNAs in the Mouse Brain.” <i>Science</i>. AAAS, 2024. <a href=\"https://doi.org/10.1126/science.adf3481\">https://doi.org/10.1126/science.adf3481</a>.","short":"S. Zocher, A. Mccloskey, A. Karasinsky, R. Schulte, U. Friedrich, M. Lesche, N. Rund, F.H. Gage, M. Hetzer, T. Toda, Science 384 (2024) 53–59.","ama":"Zocher S, Mccloskey A, Karasinsky A, et al. Lifelong persistence of nuclear RNAs in the mouse brain. <i>Science</i>. 2024;384(6691):53-59. doi:<a href=\"https://doi.org/10.1126/science.adf3481\">10.1126/science.adf3481</a>","apa":"Zocher, S., Mccloskey, A., Karasinsky, A., Schulte, R., Friedrich, U., Lesche, M., … Toda, T. (2024). Lifelong persistence of nuclear RNAs in the mouse brain. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.adf3481\">https://doi.org/10.1126/science.adf3481</a>","ieee":"S. Zocher <i>et al.</i>, “Lifelong persistence of nuclear RNAs in the mouse brain,” <i>Science</i>, vol. 384, no. 6691. AAAS, pp. 53–59, 2024."},"scopus_import":"1","acknowledgement":"European Research Council: ERC-2018-STG, 804468 EAGER; European Research Council: ERC-2023-COG, 101125034 NEUTIME; Deutsche Forschungsgemeinschaft: TO1347/4-1; Boehringer Ingelheim Stiftung; Deutsches Zentrum für Neurodegenerative Erkrankungen","OA_place":"repository","article_type":"original","OA_type":"green","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Lifelong persistence of nuclear RNAs in the mouse brain","oa":1,"abstract":[{"text":"Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.","lang":"eng"}],"publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"date_created":"2024-04-14T22:01:01Z","publication":"Science","date_updated":"2025-09-04T13:39:58Z","type":"journal_article","date_published":"2024-04-04T00:00:00Z","pmid":1,"article_processing_charge":"No","page":"53-59","publisher":"AAAS","year":"2024","_id":"15316","issue":"6691","external_id":{"isi":["001253335100031"],"pmid":["38574132"]},"isi":1,"author":[{"full_name":"Zocher, Sara","last_name":"Zocher","first_name":"Sara"},{"last_name":"Mccloskey","full_name":"Mccloskey, Asako","first_name":"Asako"},{"last_name":"Karasinsky","full_name":"Karasinsky, Anne","first_name":"Anne"},{"full_name":"Schulte, Roberta","last_name":"Schulte","first_name":"Roberta"},{"first_name":"Ulrike","full_name":"Friedrich, Ulrike","last_name":"Friedrich"},{"full_name":"Lesche, Mathias","last_name":"Lesche","first_name":"Mathias"},{"last_name":"Rund","full_name":"Rund, Nicole","first_name":"Nicole"},{"first_name":"Fred H.","last_name":"Gage","full_name":"Gage, Fred H."},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","full_name":"Hetzer, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"Hetzer"},{"first_name":"Tomohisa","last_name":"Toda","full_name":"Toda, Tomohisa"}],"intvolume":"       384","volume":384},{"article_processing_charge":"Yes","pmid":1,"date_published":"2024-10-21T00:00:00Z","year":"2024","article_number":"9063","ddc":["570"],"publisher":"Springer Nature","author":[{"first_name":"Cristiane","full_name":"Dos Santos, Cristiane","last_name":"Dos Santos"},{"first_name":"Amanda","full_name":"Cambraia, Amanda","last_name":"Cambraia"},{"first_name":"Shristi","last_name":"Shrestha","full_name":"Shrestha, Shristi"},{"last_name":"Cutler","full_name":"Cutler, Melanie","first_name":"Melanie"},{"first_name":"Matthew","full_name":"Cottam, Matthew","last_name":"Cottam"},{"first_name":"Guy","full_name":"Perkins, Guy","last_name":"Perkins"},{"full_name":"Lev-Ram, Varda","last_name":"Lev-Ram","first_name":"Varda"},{"full_name":"Roy, Birbickram","last_name":"Roy","first_name":"Birbickram"},{"last_name":"Acree","full_name":"Acree, Christopher","first_name":"Christopher"},{"first_name":"Keun Young","full_name":"Kim, Keun Young","last_name":"Kim"},{"full_name":"Deerinck, Thomas","last_name":"Deerinck","first_name":"Thomas"},{"full_name":"Dean, Danielle","last_name":"Dean","first_name":"Danielle"},{"last_name":"Cartailler","full_name":"Cartailler, Jean Philippe","first_name":"Jean Philippe"},{"first_name":"Patrick E.","last_name":"Macdonald","full_name":"Macdonald, Patrick E."},{"last_name":"Hetzer","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"Hetzer, Martin W","first_name":"Martin W","orcid":"0000-0002-2111-992X"},{"first_name":"Mark","full_name":"Ellisman, Mark","last_name":"Ellisman"},{"first_name":"Rafael","full_name":"Arrojo E Drigo, Rafael","last_name":"Arrojo E Drigo"}],"isi":1,"external_id":{"pmid":["39433757"],"isi":["001426270600023"]},"_id":"18480","volume":15,"intvolume":"        15","language":[{"iso":"eng"}],"quality_controlled":"1","oa_version":"Published Version","department":[{"_id":"MaHe"}],"publication_status":"published","day":"21","doi":"10.1038/s41467-024-53127-2","month":"10","scopus_import":"1","acknowledgement":"We are thankful to Michelle Reyzer from the Vanderbilt Mass Spectrometry Research Center for assistance with MALDI-MS imaging and analysis, to the outstanding team at the Vanderbilt Mouse Metabolic Phenotyping Center for all the assistance with in vivo glucose homeostasis tests (DK135073, 1S10RR028101-01). We also thank the University of Michigan Animal Phenotyping Core for conducting the bomb calorimetry experiments (1U2CDK110768, DK020575, and DK089503). This research was supported by recruitment funds from the Vanderbilt’s Department of Molecular Physiology and Biophysics and NIH grants 1R03DK127484, 5U24DK097771, and 1R01DK138141 to RAeD, by a grant from the Canadian Institutes of Health Research (CIHR; 487188) to PEM, by and NIH DK132669 to D.D. PEM holds the Canada Research Chair in Islet Biology.","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"citation":{"apa":"Dos Santos, C., Cambraia, A., Shrestha, S., Cutler, M., Cottam, M., Perkins, G., … Arrojo E Drigo, R. (2024). Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-024-53127-2\">https://doi.org/10.1038/s41467-024-53127-2</a>","ama":"Dos Santos C, Cambraia A, Shrestha S, et al. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. <i>Nature Communications</i>. 2024;15. doi:<a href=\"https://doi.org/10.1038/s41467-024-53127-2\">10.1038/s41467-024-53127-2</a>","ieee":"C. Dos Santos <i>et al.</i>, “Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice,” <i>Nature Communications</i>, vol. 15. Springer Nature, 2024.","ista":"Dos Santos C, Cambraia A, Shrestha S, Cutler M, Cottam M, Perkins G, Lev-Ram V, Roy B, Acree C, Kim KY, Deerinck T, Dean D, Cartailler JP, Macdonald PE, Hetzer M, Ellisman M, Arrojo E Drigo R. 2024. Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice. Nature Communications. 15, 9063.","chicago":"Dos Santos, Cristiane, Amanda Cambraia, Shristi Shrestha, Melanie Cutler, Matthew Cottam, Guy Perkins, Varda Lev-Ram, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” <i>Nature Communications</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41467-024-53127-2\">https://doi.org/10.1038/s41467-024-53127-2</a>.","mla":"Dos Santos, Cristiane, et al. “Calorie Restriction Increases Insulin Sensitivity to Promote Beta Cell Homeostasis and Longevity in Mice.” <i>Nature Communications</i>, vol. 15, 9063, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1038/s41467-024-53127-2\">10.1038/s41467-024-53127-2</a>.","short":"C. Dos Santos, A. Cambraia, S. Shrestha, M. Cutler, M. Cottam, G. Perkins, V. Lev-Ram, B. Roy, C. Acree, K.Y. Kim, T. Deerinck, D. Dean, J.P. Cartailler, P.E. Macdonald, M. Hetzer, M. Ellisman, R. Arrojo E Drigo, Nature Communications 15 (2024)."},"file":[{"success":1,"access_level":"open_access","relation":"main_file","checksum":"b936b1c047f41cd427f00e3dc79327d3","content_type":"application/pdf","file_name":"2024_NatureComm_dosSantos.pdf","date_created":"2024-11-04T10:37:56Z","file_id":"18502","file_size":7358742,"creator":"dernst","date_updated":"2024-11-04T10:37:56Z"}],"status":"public","has_accepted_license":"1","oa":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice","OA_type":"gold","article_type":"original","OA_place":"publisher","type":"journal_article","DOAJ_listed":"1","date_updated":"2025-09-08T14:32:38Z","file_date_updated":"2024-11-04T10:37:56Z","date_created":"2024-10-27T23:01:44Z","publication":"Nature Communications","publication_identifier":{"eissn":["2041-1723"]},"abstract":[{"text":"Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.","lang":"eng"}]},{"corr_author":"1","month":"04","doi":"10.1080/19491034.2023.2202548","day":"18","publication_status":"published","department":[{"_id":"MaHe"}],"oa_version":"Published Version","quality_controlled":"1","language":[{"iso":"eng"}],"status":"public","citation":{"mla":"Kaneshiro, Jeanae M., et al. “Lamin B1 Overexpression Alters Chromatin Organization and Gene Expression.” <i>Nucleus</i>, vol. 14, no. 1, 2202548, Taylor &#38; Francis, 2023, doi:<a href=\"https://doi.org/10.1080/19491034.2023.2202548\">10.1080/19491034.2023.2202548</a>.","chicago":"Kaneshiro, Jeanae M., Juliana S. Capitanio, and Martin Hetzer. “Lamin B1 Overexpression Alters Chromatin Organization and Gene Expression.” <i>Nucleus</i>. Taylor &#38; Francis, 2023. <a href=\"https://doi.org/10.1080/19491034.2023.2202548\">https://doi.org/10.1080/19491034.2023.2202548</a>.","short":"J.M. Kaneshiro, J.S. Capitanio, M. Hetzer, Nucleus 14 (2023).","ista":"Kaneshiro JM, Capitanio JS, Hetzer M. 2023. Lamin B1 overexpression alters chromatin organization and gene expression. Nucleus. 14(1), 2202548.","ieee":"J. M. Kaneshiro, J. S. Capitanio, and M. Hetzer, “Lamin B1 overexpression alters chromatin organization and gene expression,” <i>Nucleus</i>, vol. 14, no. 1. Taylor &#38; Francis, 2023.","ama":"Kaneshiro JM, Capitanio JS, Hetzer M. Lamin B1 overexpression alters chromatin organization and gene expression. <i>Nucleus</i>. 2023;14(1). doi:<a href=\"https://doi.org/10.1080/19491034.2023.2202548\">10.1080/19491034.2023.2202548</a>","apa":"Kaneshiro, J. M., Capitanio, J. S., &#38; Hetzer, M. (2023). Lamin B1 overexpression alters chromatin organization and gene expression. <i>Nucleus</i>. Taylor &#38; Francis. <a href=\"https://doi.org/10.1080/19491034.2023.2202548\">https://doi.org/10.1080/19491034.2023.2202548</a>"},"file":[{"file_name":"2023_Nucleus_Kaneshiro.pdf","date_created":"2023-05-02T07:24:55Z","file_id":"12884","file_size":3811113,"creator":"dernst","date_updated":"2023-05-02T07:24:55Z","success":1,"access_level":"open_access","relation":"main_file","checksum":"8e707eda84f64dbad7f03545ae0a83ef","content_type":"application/pdf"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"scopus_import":"1","acknowledgement":"We thank members of the Hetzer lab for critical review of the manuscript; Novogene for mRNA library preparation and sequencing; the Next-Generation Sequencing Core Facility at the Salk Institute, with funding from NIH-NCI CCSG: P30 014195, the Chapman Foundation, and the Helmsley Charitable Trust, for sequencing Cut&Run libraries; and the Waitt Advanced Biophotonics Core Facility at the Salk Institute, with funding from NIH-NCI CCSG: P30 014195, the Waitt Foundation, and the Chan-Zuckerberg Initiative Imaging Scientist Award, for electron microscopy sample preparation and imaging.","article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Lamin B1 overexpression alters chromatin organization and gene expression","oa":1,"has_accepted_license":"1","abstract":[{"text":"Peripheral heterochromatin positioning depends on nuclear envelope associated proteins and repressive histone modifications. Here we show that overexpression (OE) of Lamin B1 (LmnB1) leads to the redistribution of peripheral heterochromatin into heterochromatic foci within the nucleoplasm. These changes represent a perturbation of heterochromatin binding at the nuclear periphery (NP) through a mechanism independent from altering other heterochromatin anchors or histone post-translational modifications. We further show that LmnB1 OE alters gene expression. These changes do not correlate with different levels of H3K9me3, but a significant number of the misregulated genes were likely mislocalized away from the NP upon LmnB1 OE. We also observed an enrichment of developmental processes amongst the upregulated genes. ~74% of these genes were normally repressed in our cell type, suggesting that LmnB1 OE promotes gene de-repression. This demonstrates a broader consequence of LmnB1 OE on cell fate, and highlights the importance of maintaining proper levels of LmnB1.","lang":"eng"}],"publication_identifier":{"issn":["1949-1034"],"eissn":["1949-1042"]},"publication":"Nucleus","date_created":"2023-04-30T22:01:06Z","license":"https://creativecommons.org/licenses/by-nc/4.0/","file_date_updated":"2023-05-02T07:24:55Z","date_updated":"2024-10-09T21:05:01Z","type":"journal_article","pmid":1,"date_published":"2023-04-18T00:00:00Z","article_processing_charge":"No","publisher":"Taylor & Francis","ddc":["570"],"article_number":"2202548","year":"2023","issue":"1","_id":"12880","external_id":{"isi":["000971629400001"],"pmid":["37071033"]},"author":[{"first_name":"Jeanae M.","full_name":"Kaneshiro, Jeanae M.","last_name":"Kaneshiro"},{"full_name":"Capitanio, Juliana S.","last_name":"Capitanio","first_name":"Juliana S."},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","last_name":"Hetzer","full_name":"Hetzer, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed"}],"isi":1,"intvolume":"        14","volume":14},{"day":"04","doi":"10.7554/eLife.89066","department":[{"_id":"MaHe"}],"publication_status":"published","month":"09","corr_author":"1","language":[{"iso":"eng"}],"oa_version":"Published Version","quality_controlled":"1","file":[{"file_size":3703097,"creator":"dernst","date_updated":"2023-09-15T06:59:10Z","file_name":"2023_eLife_Cho.pdf","file_id":"14336","date_created":"2023-09-15T06:59:10Z","relation":"main_file","checksum":"db24bf3d595507387b48d3799c33e289","content_type":"application/pdf","success":1,"access_level":"open_access"}],"citation":{"ista":"Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066.","mla":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>, vol. 12, RP89066, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>.","chicago":"Cho, Ukrae H., and Martin Hetzer. “Caspase-Mediated Nuclear Pore Complex Trimming in Cell Differentiation and Endoplasmic Reticulum Stress.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>.","short":"U.H. Cho, M. Hetzer, ELife 12 (2023).","ama":"Cho UH, Hetzer M. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>eLife</i>. 2023;12. doi:<a href=\"https://doi.org/10.7554/eLife.89066\">10.7554/eLife.89066</a>","apa":"Cho, U. H., &#38; Hetzer, M. (2023). Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.89066\">https://doi.org/10.7554/eLife.89066</a>","ieee":"U. H. Cho and M. Hetzer, “Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2023."},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"status":"public","acknowledgement":"We thank the members of the Hetzer laboratory, Tony Hunter (Salk), Lorenzo Puri (Sanford Burnham Prebys), and Jongmin Kim (Massachusetts General Hospital) for the critical reading of the manuscript; Kenneth Diffenderfer and Aimee Pankonin (Stem Cell Core at the Salk Institute) for help with neurogenesis; Carol Marchetto and Fred Gage (Salk) for providing H9 embryonic stem cells; Lorenzo Puri, Alexandra Sacco, and Luca Caputo (Sanford Burnham Prebys) for helpful discussions and sharing mouse primary myoblasts. This work was supported by a Glenn Foundation for Medical Research Postdoctoral Fellowship in Aging Research (UHC), the NOMIS foundation (MWH), and the National Institutes of Health (R01 NS096786 to MWH and K01 AR080828 to UHC). This work was also supported by the Mass Spectrometry Core of the Salk Institute with funding from NIH-NCI CCSG: P30 014195 and the Helmsley Center for Genomic Medicine. We thank Jolene Diedrich and Antonio Pinto for technical support.","scopus_import":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress","article_type":"original","oa":1,"has_accepted_license":"1","publication_identifier":{"eissn":["2050-084X"]},"date_created":"2023-09-10T22:01:11Z","publication":"eLife","abstract":[{"lang":"eng","text":"During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels."}],"date_updated":"2024-10-09T21:06:57Z","type":"journal_article","file_date_updated":"2023-09-15T06:59:10Z","pmid":1,"date_published":"2023-09-04T00:00:00Z","article_processing_charge":"Yes","ddc":["570"],"publisher":"eLife Sciences Publications","article_number":"RP89066","year":"2023","external_id":{"pmid":["37665327"]},"_id":"14315","author":[{"last_name":"Cho","full_name":"Cho, Ukrae H.","first_name":"Ukrae H."},{"first_name":"Martin W","orcid":"0000-0002-2111-992X","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"Hetzer, Martin W","last_name":"Hetzer"}],"intvolume":"        12","volume":12},{"abstract":[{"text":"The role of nuclear pore complexes (NPCs) in genome organization remains poorly characterized due to technical limitations in probing genome-wide protein-DNA interactions specific to the nuclear periphery. Here, we developed a new sensitive method, NPC-DamID, which combines in vitro reconstitution of nuclear import and DamID technology. The fixation-free method identifies chromatin interactions at the NPCs in intact nuclei from cells and tissues. We found that NPCs are preferentially associated with common and hierarchically arranged super-enhancers (SEs) across multiple cell types. We also uncovered phase-separated condensates at NPCs that compartmentalize and concentrate transcriptional coactivators and structural proteins at SE-regulated genes. Our results support NPCs as anchoring sites for SE regulatory hubs and cell-type-specific transcriptional control.","lang":"eng"}],"date_created":"2024-01-22T12:21:56Z","publication":"eLife","type":"journal_article","date_updated":"2024-07-31T11:56:25Z","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope","_id":"14868","author":[{"last_name":"Tyagi","full_name":"Tyagi, Swati","first_name":"Swati"},{"last_name":"Capitanio","full_name":"Capitanio, Juliana S.","first_name":"Juliana S."},{"first_name":"Jiawei","full_name":"Xu, Jiawei","last_name":"Xu"},{"first_name":"Fei","last_name":"Chen","full_name":"Chen, Fei"},{"first_name":"Rahul","last_name":"Sharma","full_name":"Sharma, Rahul"},{"first_name":"Jialiang","full_name":"Huang, Jialiang","last_name":"Huang"},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"oa":1,"main_file_link":[{"url":"https://doi.org/10.7554/eLife.87462.1","open_access":"1"}],"status":"public","publisher":"eLife Sciences Publications","citation":{"ama":"Tyagi S, Capitanio JS, Xu J, et al. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. <i>eLife</i>. 2023. doi:<a href=\"https://doi.org/10.7554/elife.87462\">10.7554/elife.87462</a>","apa":"Tyagi, S., Capitanio, J. S., Xu, J., Chen, F., Sharma, R., Huang, J., &#38; Hetzer, M. (2023). High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.87462\">https://doi.org/10.7554/elife.87462</a>","ieee":"S. Tyagi <i>et al.</i>, “High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope,” <i>eLife</i>. eLife Sciences Publications, 2023.","ista":"Tyagi S, Capitanio JS, Xu J, Chen F, Sharma R, Huang J, Hetzer M. 2023. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. eLife.","chicago":"Tyagi, Swati, Juliana S. Capitanio, Jiawei Xu, Fei Chen, Rahul Sharma, Jialiang Huang, and Martin Hetzer. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” <i>ELife</i>. eLife Sciences Publications, 2023. <a href=\"https://doi.org/10.7554/elife.87462\">https://doi.org/10.7554/elife.87462</a>.","short":"S. Tyagi, J.S. Capitanio, J. Xu, F. Chen, R. Sharma, J. Huang, M. Hetzer, ELife (2023).","mla":"Tyagi, Swati, et al. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” <i>ELife</i>, eLife Sciences Publications, 2023, doi:<a href=\"https://doi.org/10.7554/elife.87462\">10.7554/elife.87462</a>."},"year":"2023","acknowledgement":"This work was supported by M.H.’s NIH R01 grants (NS096786, GM126829) and Salk Cancer Center Support Grant P30 CA014195. M.H. also received financial support from the W.M. Keck Foundation and the NOMIS Foundation. Further, M.H. received support from the AHA-Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and The Paul G. Allen Frontiers Group (19PABH134610000).\r\n\r\nS.T. and J.C. were supported by Salk’s Women & Science Awards. S.T. also received financial support from the Hewitt Foundation fellowship, and J.C. is a Paul F. Glenn Biology of Aging fellow. J.H. was supported by the National Natural Science Foundation of China (31871317 and 32070635).\r\n\r\nWe thank Roberta Schulte for assistance with in vitro transport assays, for comments that greatly improved the manuscript, and for helping refine the figures presented in this work. We thank Shefali Krishna for creating the diagram for the NPC-DamID method, for her input on super-resolution microscopy analysis, and her insightful comments on this manuscript. We thank all members of the Hetzer lab for helpful discussions of these research ideas and their thoughtful comments on this manuscript. We are also grateful to Salk’s core facilities for their assistance. Specifically, we thank the Next Generation Sequencing Core (NGS) for sequencing our DamID and RNA NGS libraries, the Advanced Biophotonics Core for assistance with super-resolution microscopy, and the Razavi Newman Integrative Genomics and Bioinformatics Core (IGC) for their input on analysis methods for DamID experiments.","corr_author":"1","month":"06","date_published":"2023-06-23T00:00:00Z","publication_status":"epub_ahead","department":[{"_id":"MaHe"}],"doi":"10.7554/elife.87462","day":"23","article_processing_charge":"Yes","oa_version":"Submitted Version","language":[{"iso":"eng"}]},{"author":[{"first_name":"Shefali","full_name":"Krishna, Shefali","last_name":"Krishna"},{"full_name":"Arrojo e Drigo, Rafael","last_name":"Arrojo e Drigo","first_name":"Rafael"},{"first_name":"Juliana S.","full_name":"Capitanio, Juliana S.","last_name":"Capitanio"},{"first_name":"Ranjan","full_name":"Ramachandra, Ranjan","last_name":"Ramachandra"},{"first_name":"Mark","last_name":"Ellisman","full_name":"Ellisman, Mark"},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER"}],"_id":"11052","external_id":{"pmid":["34715012"]},"issue":"21","extern":"1","volume":56,"intvolume":"        56","article_processing_charge":"No","page":"P2952-2965.e9","pmid":1,"date_published":"2021-11-08T00:00:00Z","year":"2021","publisher":"Elsevier","keyword":["Developmental Biology","Cell Biology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology"],"article_type":"original","title":"Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","date_updated":"2025-12-15T10:01:56Z","abstract":[{"text":"In order to combat molecular damage, most cellular proteins undergo rapid turnover. We have previously identified large nuclear protein assemblies that can persist for years in post-mitotic tissues and are subject to age-related decline. Here, we report that mitochondria can be long lived in the mouse brain and reveal that specific mitochondrial proteins have half-lives longer than the average proteome. These mitochondrial long-lived proteins (mitoLLPs) are core components of the electron transport chain (ETC) and display increased longevity in respiratory supercomplexes. We find that COX7C, a mitoLLP that forms a stable contact site between complexes I and IV, is required for complex IV and supercomplex assembly. Remarkably, even upon depletion of COX7C transcripts, ETC function is maintained for days, effectively uncoupling mitochondrial function from ongoing transcription of its mitoLLPs. Our results suggest that modulating protein longevity within the ETC is critical for mitochondrial proteome maintenance and the robustness of mitochondrial function.","lang":"eng"}],"date_created":"2022-04-07T07:43:14Z","publication":"Developmental Cell","publication_identifier":{"issn":["1534-5807"]},"language":[{"iso":"eng"}],"quality_controlled":"1","oa_version":"None","month":"11","department":[{"_id":"MaHe"}],"publication_status":"published","doi":"10.1016/j.devcel.2021.10.008","day":"08","scopus_import":"1","status":"public","citation":{"ieee":"S. Krishna, R. Arrojo e Drigo, J. S. Capitanio, R. Ramachandra, M. Ellisman, and M. Hetzer, “Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain,” <i>Developmental Cell</i>, vol. 56, no. 21. Elsevier, p. P2952–2965.e9, 2021.","apa":"Krishna, S., Arrojo e Drigo, R., Capitanio, J. S., Ramachandra, R., Ellisman, M., &#38; Hetzer, M. (2021). Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">https://doi.org/10.1016/j.devcel.2021.10.008</a>","ama":"Krishna S, Arrojo e Drigo R, Capitanio JS, Ramachandra R, Ellisman M, Hetzer M. Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. <i>Developmental Cell</i>. 2021;56(21):P2952-2965.e9. doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">10.1016/j.devcel.2021.10.008</a>","chicago":"Krishna, Shefali, Rafael Arrojo e Drigo, Juliana S. Capitanio, Ranjan Ramachandra, Mark Ellisman, and Martin Hetzer. “Identification of Long-Lived Proteins in the Mitochondria Reveals Increased Stability of the Electron Transport Chain.” <i>Developmental Cell</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">https://doi.org/10.1016/j.devcel.2021.10.008</a>.","short":"S. Krishna, R. Arrojo e Drigo, J.S. Capitanio, R. Ramachandra, M. Ellisman, M. Hetzer, Developmental Cell 56 (2021) P2952–2965.e9.","mla":"Krishna, Shefali, et al. “Identification of Long-Lived Proteins in the Mitochondria Reveals Increased Stability of the Electron Transport Chain.” <i>Developmental Cell</i>, vol. 56, no. 21, Elsevier, 2021, p. P2952–2965.e9, doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.10.008\">10.1016/j.devcel.2021.10.008</a>.","ista":"Krishna S, Arrojo e Drigo R, Capitanio JS, Ramachandra R, Ellisman M, Hetzer M. 2021. Identification of long-lived proteins in the mitochondria reveals increased stability of the electron transport chain. Developmental Cell. 56(21), P2952–2965.e9."}},{"date_published":"2019-08-06T00:00:00Z","pmid":1,"article_processing_charge":"No","page":"343-351.e3","publisher":"Elsevier","year":"2019","_id":"11062","extern":"1","external_id":{"pmid":["31178361"]},"issue":"2","author":[{"first_name":"Rafael","last_name":"Arrojo e Drigo","full_name":"Arrojo e Drigo, Rafael"},{"full_name":"Lev-Ram, Varda","last_name":"Lev-Ram","first_name":"Varda"},{"first_name":"Swati","last_name":"Tyagi","full_name":"Tyagi, Swati"},{"full_name":"Ramachandra, Ranjan","last_name":"Ramachandra","first_name":"Ranjan"},{"last_name":"Deerinck","full_name":"Deerinck, Thomas","first_name":"Thomas"},{"first_name":"Eric","last_name":"Bushong","full_name":"Bushong, Eric"},{"first_name":"Sebastien","last_name":"Phan","full_name":"Phan, Sebastien"},{"last_name":"Orphan","full_name":"Orphan, Victoria","first_name":"Victoria"},{"first_name":"Claude","full_name":"Lechene, Claude","last_name":"Lechene"},{"first_name":"Mark H.","last_name":"Ellisman","full_name":"Ellisman, Mark H."},{"full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER","orcid":"0000-0002-2111-992X","first_name":"Martin W"}],"intvolume":"        30","volume":30,"month":"08","doi":"10.1016/j.cmet.2019.05.010","day":"06","department":[{"_id":"MaHe"}],"publication_status":"published","quality_controlled":"1","language":[{"iso":"eng"}],"oa_version":"Published Version","status":"public","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cmet.2019.05.010"}],"citation":{"apa":"Arrojo e Drigo, R., Lev-Ram, V., Tyagi, S., Ramachandra, R., Deerinck, T., Bushong, E., … Hetzer, M. (2019). Age mosaicism across multiple scales in adult tissues. <i>Cell Metabolism</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">https://doi.org/10.1016/j.cmet.2019.05.010</a>","ama":"Arrojo e Drigo R, Lev-Ram V, Tyagi S, et al. Age mosaicism across multiple scales in adult tissues. <i>Cell Metabolism</i>. 2019;30(2):343-351.e3. doi:<a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">10.1016/j.cmet.2019.05.010</a>","ieee":"R. Arrojo e Drigo <i>et al.</i>, “Age mosaicism across multiple scales in adult tissues,” <i>Cell Metabolism</i>, vol. 30, no. 2. Elsevier, p. 343–351.e3, 2019.","ista":"Arrojo e Drigo R, Lev-Ram V, Tyagi S, Ramachandra R, Deerinck T, Bushong E, Phan S, Orphan V, Lechene C, Ellisman MH, Hetzer M. 2019. Age mosaicism across multiple scales in adult tissues. Cell Metabolism. 30(2), 343–351.e3.","chicago":"Arrojo e Drigo, Rafael, Varda Lev-Ram, Swati Tyagi, Ranjan Ramachandra, Thomas Deerinck, Eric Bushong, Sebastien Phan, et al. “Age Mosaicism across Multiple Scales in Adult Tissues.” <i>Cell Metabolism</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">https://doi.org/10.1016/j.cmet.2019.05.010</a>.","short":"R. Arrojo e Drigo, V. Lev-Ram, S. Tyagi, R. Ramachandra, T. Deerinck, E. Bushong, S. Phan, V. Orphan, C. Lechene, M.H. Ellisman, M. Hetzer, Cell Metabolism 30 (2019) 343–351.e3.","mla":"Arrojo e Drigo, Rafael, et al. “Age Mosaicism across Multiple Scales in Adult Tissues.” <i>Cell Metabolism</i>, vol. 30, no. 2, Elsevier, 2019, p. 343–351.e3, doi:<a href=\"https://doi.org/10.1016/j.cmet.2019.05.010\">10.1016/j.cmet.2019.05.010</a>."},"scopus_import":"1","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Age mosaicism across multiple scales in adult tissues","keyword":["Cell Biology","Molecular Biology","Physiology"],"oa":1,"abstract":[{"text":"Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using 15N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization.","lang":"eng"}],"publication_identifier":{"issn":["1550-4131"]},"date_created":"2022-04-07T07:45:21Z","publication":"Cell Metabolism","date_updated":"2025-12-15T10:02:11Z","type":"journal_article"},{"volume":154,"intvolume":"       154","author":[{"full_name":"Toyama, Brandon H.","last_name":"Toyama","first_name":"Brandon H."},{"first_name":"Jeffrey N.","full_name":"Savas, Jeffrey N.","last_name":"Savas"},{"full_name":"Park, Sung Kyu","last_name":"Park","first_name":"Sung Kyu"},{"first_name":"Michael S.","last_name":"Harris","full_name":"Harris, Michael S."},{"first_name":"Nicholas T.","full_name":"Ingolia, Nicholas T.","last_name":"Ingolia"},{"first_name":"John R.","full_name":"Yates, John R.","last_name":"Yates"},{"first_name":"Martin W","orcid":"0000-0002-2111-992X","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"HETZER, Martin W"}],"extern":"1","_id":"11087","issue":"5","external_id":{"pmid":["23993091"]},"year":"2013","publisher":"Elsevier","article_processing_charge":"No","page":"971-982","pmid":1,"date_published":"2013-08-29T00:00:00Z","date_updated":"2025-12-15T10:02:46Z","type":"journal_article","abstract":[{"text":"Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell’s life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process.","lang":"eng"}],"publication_identifier":{"issn":["0092-8674"]},"date_created":"2022-04-07T07:51:08Z","publication":"Cell","keyword":["General Biochemistry","Genetics and Molecular Biology"],"oa":1,"article_type":"original","title":"Identification of long-lived proteins reveals exceptional stability of essential cellular structures","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1016/j.cell.2013.07.037","open_access":"1"}],"status":"public","citation":{"ista":"Toyama BH, Savas JN, Park SK, Harris MS, Ingolia NT, Yates JR, Hetzer M. 2013. Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell. 154(5), 971–982.","chicago":"Toyama, Brandon H., Jeffrey N. Savas, Sung Kyu Park, Michael S. Harris, Nicholas T. Ingolia, John R. Yates, and Martin Hetzer. “Identification of Long-Lived Proteins Reveals Exceptional Stability of Essential Cellular Structures.” <i>Cell</i>. Elsevier, 2013. <a href=\"https://doi.org/10.1016/j.cell.2013.07.037\">https://doi.org/10.1016/j.cell.2013.07.037</a>.","short":"B.H. Toyama, J.N. Savas, S.K. Park, M.S. Harris, N.T. Ingolia, J.R. Yates, M. Hetzer, Cell 154 (2013) 971–982.","mla":"Toyama, Brandon H., et al. “Identification of Long-Lived Proteins Reveals Exceptional Stability of Essential Cellular Structures.” <i>Cell</i>, vol. 154, no. 5, Elsevier, 2013, pp. 971–82, doi:<a href=\"https://doi.org/10.1016/j.cell.2013.07.037\">10.1016/j.cell.2013.07.037</a>.","apa":"Toyama, B. H., Savas, J. N., Park, S. K., Harris, M. S., Ingolia, N. T., Yates, J. R., &#38; Hetzer, M. (2013). Identification of long-lived proteins reveals exceptional stability of essential cellular structures. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2013.07.037\">https://doi.org/10.1016/j.cell.2013.07.037</a>","ama":"Toyama BH, Savas JN, Park SK, et al. Identification of long-lived proteins reveals exceptional stability of essential cellular structures. <i>Cell</i>. 2013;154(5):971-982. doi:<a href=\"https://doi.org/10.1016/j.cell.2013.07.037\">10.1016/j.cell.2013.07.037</a>","ieee":"B. H. Toyama <i>et al.</i>, “Identification of long-lived proteins reveals exceptional stability of essential cellular structures,” <i>Cell</i>, vol. 154, no. 5. Elsevier, pp. 971–982, 2013."},"language":[{"iso":"eng"}],"oa_version":"Published Version","quality_controlled":"1","month":"08","doi":"10.1016/j.cell.2013.07.037","day":"29","publication_status":"published","department":[{"_id":"MaHe"}]},{"date_created":"2022-04-07T07:52:01Z","publication":"Science","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"abstract":[{"text":"To combat the functional decline of the proteome, cells use the process of protein turnover to replace potentially impaired polypeptides with new functional copies. We found that extremely long-lived proteins (ELLPs) did not turn over in postmitotic cells of the rat central nervous system. These ELLPs were associated with chromatin and the nuclear pore complex, the central transport channels that mediate all molecular trafficking in and out of the nucleus. The longevity of these proteins would be expected to expose them to potentially harmful metabolites, putting them at risk of accumulating damage over extended periods of time. Thus, it is possible that failure to maintain proper levels and functional integrity of ELLPs in nonproliferative cells might contribute to age-related deterioration in cell and tissue function.","lang":"eng"}],"type":"journal_article","date_updated":"2025-12-15T10:03:06Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Extremely long-lived nuclear pore proteins in the rat brain","article_type":"letter_note","citation":{"mla":"Savas, Jeffrey N., et al. “Extremely Long-Lived Nuclear Pore Proteins in the Rat Brain.” <i>Science</i>, vol. 335, no. 6071, American Association for the Advancement of Science, 2012, pp. 942–942, doi:<a href=\"https://doi.org/10.1126/science.1217421\">10.1126/science.1217421</a>.","short":"J.N. Savas, B.H. Toyama, T. Xu, J.R. Yates, M. Hetzer, Science 335 (2012) 942–942.","chicago":"Savas, Jeffrey N., Brandon H. Toyama, Tao Xu, John R. Yates, and Martin Hetzer. “Extremely Long-Lived Nuclear Pore Proteins in the Rat Brain.” <i>Science</i>. American Association for the Advancement of Science, 2012. <a href=\"https://doi.org/10.1126/science.1217421\">https://doi.org/10.1126/science.1217421</a>.","ista":"Savas JN, Toyama BH, Xu T, Yates JR, Hetzer M. 2012. Extremely long-lived nuclear pore proteins in the rat brain. Science. 335(6071), 942–942.","ieee":"J. N. Savas, B. H. Toyama, T. Xu, J. R. Yates, and M. Hetzer, “Extremely long-lived nuclear pore proteins in the rat brain,” <i>Science</i>, vol. 335, no. 6071. American Association for the Advancement of Science, pp. 942–942, 2012.","ama":"Savas JN, Toyama BH, Xu T, Yates JR, Hetzer M. Extremely long-lived nuclear pore proteins in the rat brain. <i>Science</i>. 2012;335(6071):942-942. doi:<a href=\"https://doi.org/10.1126/science.1217421\">10.1126/science.1217421</a>","apa":"Savas, J. N., Toyama, B. H., Xu, T., Yates, J. R., &#38; Hetzer, M. (2012). Extremely long-lived nuclear pore proteins in the rat brain. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.1217421\">https://doi.org/10.1126/science.1217421</a>"},"status":"public","scopus_import":"1","publication_status":"published","department":[{"_id":"MaHe"}],"doi":"10.1126/science.1217421","day":"02","month":"02","language":[{"iso":"eng"}],"oa_version":"None","quality_controlled":"1","intvolume":"       335","volume":335,"_id":"11092","issue":"6071","extern":"1","external_id":{"pmid":["22300851"]},"author":[{"first_name":"Jeffrey N.","full_name":"Savas, Jeffrey N.","last_name":"Savas"},{"full_name":"Toyama, Brandon H.","last_name":"Toyama","first_name":"Brandon H."},{"last_name":"Xu","full_name":"Xu, Tao","first_name":"Tao"},{"first_name":"John R.","last_name":"Yates","full_name":"Yates, John R."},{"last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"HETZER, Martin W","first_name":"Martin W","orcid":"0000-0002-2111-992X"}],"publisher":"American Association for the Advancement of Science","year":"2012","pmid":1,"date_published":"2012-02-02T00:00:00Z","page":"942-942","article_processing_charge":"No"}]