{"date_updated":"2025-11-04T14:58:42Z","oa_version":"Published Version","quality_controlled":"1","oa":1,"PlanS_conform":"1","title":"TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence","author":[{"first_name":"Jennifer","last_name":"Kahlhofer","full_name":"Kahlhofer, Jennifer"},{"full_name":"Marchet, Nikolas","last_name":"Marchet","first_name":"Nikolas"},{"full_name":"Zubak, Kristian","last_name":"Zubak","first_name":"Kristian"},{"full_name":"Seifert, Brigitta","last_name":"Seifert","first_name":"Brigitta"},{"first_name":"Madlen","last_name":"Hotze","full_name":"Hotze, Madlen"},{"full_name":"Egger-Hörschinger, Anna-Sophia","last_name":"Egger-Hörschinger","first_name":"Anna-Sophia"},{"first_name":"Lucija","last_name":"Kucej","full_name":"Kucej, Lucija"},{"full_name":"Manzl, Claudia","last_name":"Manzl","first_name":"Claudia"},{"first_name":"Yannick","last_name":"Weyer","full_name":"Weyer, Yannick"},{"first_name":"Sabine","full_name":"Weys, Sabine","last_name":"Weys","id":"caffa136-9669-11ed-9092-ceac12ac9c05"},{"last_name":"Offterdinger","full_name":"Offterdinger, Martin","first_name":"Martin"},{"full_name":"Herzog, Sebastian","last_name":"Herzog","first_name":"Sebastian"},{"first_name":"Veronika","last_name":"Reiterer","full_name":"Reiterer, Veronika"},{"first_name":"Chiara","last_name":"Volani","full_name":"Volani, Chiara"},{"full_name":"Kwiatkowski, Marcel","last_name":"Kwiatkowski","first_name":"Marcel"},{"first_name":"Saskia B","full_name":"Wortmann, Saskia B","last_name":"Wortmann"},{"first_name":"Siamak","full_name":"Nemati, Siamak","last_name":"Nemati"},{"first_name":"Johannes A","full_name":"Mayr, Johannes A","last_name":"Mayr"},{"last_name":"Zschocke","full_name":"Zschocke, Johannes","first_name":"Johannes"},{"full_name":"Radlinger, Bernhard","last_name":"Radlinger","first_name":"Bernhard"},{"full_name":"Thedieck, Kathrin","last_name":"Thedieck","first_name":"Kathrin"},{"last_name":"Kremser","full_name":"Kremser, Leopold","first_name":"Leopold"},{"last_name":"Sarg","full_name":"Sarg, Bettina","first_name":"Bettina"},{"full_name":"Huber, Lukas A","last_name":"Huber","first_name":"Lukas A"},{"first_name":"Hesso","last_name":"Farhan","full_name":"Farhan, Hesso"},{"first_name":"Mariana E G","last_name":"de Araujo","full_name":"de Araujo, Mariana E G"},{"last_name":"Kaser","full_name":"Kaser, Susanne","first_name":"Susanne"},{"full_name":"Scholl-Bürgi, Sabine","last_name":"Scholl-Bürgi","first_name":"Sabine"},{"last_name":"Karall","full_name":"Karall, Daniela","first_name":"Daniela"},{"last_name":"Teis","full_name":"Teis, David","first_name":"David"}],"abstract":[{"text":"Entry into and exit from cellular quiescence require dynamic adjustments in nutrient acquisition, yet the mechanisms by which quiescent cells downregulate amino acid (AA) transport remain poorly understood. Here we show that cells entering quiescence selectively target plasma membrane-resident amino acid transporters for endocytosis and lysosomal degradation. This process matches amino acid uptake with reduced translational demand and promotes survival during extended periods of quiescence. Mechanistically, we identify the α-arrestin TXNIP as a key regulator of this metabolic adaptation, since it mediates the endocytosis of the SLC7A5-SLC3A2 (LAT1-4F2hc) AA transporter complex in response to reduced AKT signaling. To promote transporter ubiquitination, TXNIP interacts with NEDD4L and other HECT-type ubiquitin ligases. Loss of TXNIP disrupts this regulation, resulting in dysregulated amino acid uptake, sustained mTORC1 signaling, and ultimately cell death under prolonged quiescence. The characterization of a novel TXNIP loss-of-function variant in a patient with a severe metabolic disease further supports its role in nutrient homeostasis and human health. Together, these findings highlight TXNIP’s central role in controlling nutrient acquisition and metabolic plasticity with implications for quiescence biology and diseases.","lang":"eng"}],"has_accepted_license":"1","OA_type":"gold","year":"2025","department":[{"_id":"MaHe"}],"month":"10","main_file_link":[{"url":"https://doi.org/10.1038/s44318-025-00608-9","open_access":"1"}],"citation":{"mla":"Kahlhofer, Jennifer, et al. “TXNIP Mediates LAT1/SLC7A5 Endocytosis to Limit Amino Acid Uptake in Cells Entering Quiescence.” <i>The EMBO Journal</i>, Embo Press, 2025, doi:<a href=\"https://doi.org/10.1038/s44318-025-00608-9\">10.1038/s44318-025-00608-9</a>.","chicago":"Kahlhofer, Jennifer, Nikolas Marchet, Kristian Zubak, Brigitta Seifert, Madlen Hotze, Anna-Sophia Egger-Hörschinger, Lucija Kucej, et al. “TXNIP Mediates LAT1/SLC7A5 Endocytosis to Limit Amino Acid Uptake in Cells Entering Quiescence.” <i>The EMBO Journal</i>. Embo Press, 2025. <a href=\"https://doi.org/10.1038/s44318-025-00608-9\">https://doi.org/10.1038/s44318-025-00608-9</a>.","apa":"Kahlhofer, J., Marchet, N., Zubak, K., Seifert, B., Hotze, M., Egger-Hörschinger, A.-S., … Teis, D. (2025). TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence. <i>The EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.1038/s44318-025-00608-9\">https://doi.org/10.1038/s44318-025-00608-9</a>","ista":"Kahlhofer J, Marchet N, Zubak K, Seifert B, Hotze M, Egger-Hörschinger A-S, Kucej L, Manzl C, Weyer Y, Weys S, Offterdinger M, Herzog S, Reiterer V, Volani C, Kwiatkowski M, Wortmann SB, Nemati S, Mayr JA, Zschocke J, Radlinger B, Thedieck K, Kremser L, Sarg B, Huber LA, Farhan H, de Araujo MEG, Kaser S, Scholl-Bürgi S, Karall D, Teis D. 2025. TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence. The EMBO Journal.","ama":"Kahlhofer J, Marchet N, Zubak K, et al. TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence. <i>The EMBO Journal</i>. 2025. doi:<a href=\"https://doi.org/10.1038/s44318-025-00608-9\">10.1038/s44318-025-00608-9</a>","ieee":"J. Kahlhofer <i>et al.</i>, “TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence,” <i>The EMBO Journal</i>. Embo Press, 2025.","short":"J. Kahlhofer, N. Marchet, K. Zubak, B. Seifert, M. Hotze, A.-S. Egger-Hörschinger, L. Kucej, C. Manzl, Y. Weyer, S. Weys, M. Offterdinger, S. Herzog, V. Reiterer, C. Volani, M. Kwiatkowski, S.B. Wortmann, S. Nemati, J.A. Mayr, J. Zschocke, B. Radlinger, K. Thedieck, L. Kremser, B. Sarg, L.A. Huber, H. Farhan, M.E.G. de Araujo, S. Kaser, S. Scholl-Bürgi, D. Karall, D. Teis, The EMBO Journal (2025)."},"ddc":["570"],"DOAJ_listed":"1","scopus_import":"1","status":"public","language":[{"iso":"eng"}],"publication":"The EMBO Journal","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1460-2075"]},"publication_status":"epub_ahead","pmid":1,"publisher":"Embo Press","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"date_created":"2025-11-04T14:34:29Z","article_type":"original","type":"journal_article","date_published":"2025-10-20T00:00:00Z","day":"20","article_processing_charge":"Yes","doi":"10.1038/s44318-025-00608-9","OA_place":"publisher","external_id":{"pmid":["41116060"]},"_id":"20604"}