{"citation":{"apa":"Boytsov, D., Madej, G. M., Horn, G., Blaha, N., Köcher, T., Sitte, H. H., … Roblek, M. (2024). Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2319686121\">https://doi.org/10.1073/pnas.2319686121</a>","mla":"Boytsov, Danila, et al. “Orphan Lysosomal Solute Carrier MFSD1 Facilitates Highly Selective Dipeptide Transport.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 13, e2319686121, Proceedings of the National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2319686121\">10.1073/pnas.2319686121</a>.","ieee":"D. Boytsov <i>et al.</i>, “Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 13. Proceedings of the National Academy of Sciences, 2024.","short":"D. Boytsov, G.M. Madej, G. Horn, N. Blaha, T. Köcher, H.H. Sitte, D.E. Siekhaus, C. Ziegler, W. Sandtner, M. Roblek, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","chicago":"Boytsov, Danila, Gregor M. Madej, Georg Horn, Nadine Blaha, Thomas Köcher, Harald H. Sitte, Daria E Siekhaus, Christine Ziegler, Walter Sandtner, and Marko Roblek. “Orphan Lysosomal Solute Carrier MFSD1 Facilitates Highly Selective Dipeptide Transport.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2319686121\">https://doi.org/10.1073/pnas.2319686121</a>.","ista":"Boytsov D, Madej GM, Horn G, Blaha N, Köcher T, Sitte HH, Siekhaus DE, Ziegler C, Sandtner W, Roblek M. 2024. Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport. Proceedings of the National Academy of Sciences of the United States of America. 121(13), e2319686121.","ama":"Boytsov D, Madej GM, Horn G, et al. Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(13). doi:<a href=\"https://doi.org/10.1073/pnas.2319686121\">10.1073/pnas.2319686121</a>"},"publication_status":"published","pmid":1,"scopus_import":"1","_id":"15250","title":"Orphan lysosomal solute carrier MFSD1 facilitates highly selective dipeptide transport","ddc":["570"],"intvolume":"       121","volume":121,"publisher":"Proceedings of the National Academy of Sciences","author":[{"first_name":"Danila","full_name":"Boytsov, Danila","last_name":"Boytsov"},{"full_name":"Madej, Gregor M.","first_name":"Gregor M.","last_name":"Madej"},{"last_name":"Horn","first_name":"Georg","full_name":"Horn, Georg"},{"last_name":"Blaha","full_name":"Blaha, Nadine","first_name":"Nadine"},{"last_name":"Köcher","full_name":"Köcher, Thomas","first_name":"Thomas"},{"last_name":"Sitte","full_name":"Sitte, Harald H.","first_name":"Harald H."},{"last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353"},{"full_name":"Ziegler, Christine","first_name":"Christine","last_name":"Ziegler"},{"first_name":"Walter","full_name":"Sandtner, Walter","last_name":"Sandtner"},{"orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","full_name":"Roblek, Marko","first_name":"Marko","last_name":"Roblek"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","license":"https://creativecommons.org/licenses/by/4.0/","oa_version":"Published Version","month":"03","publication_identifier":{"eissn":["1091-6490"]},"quality_controlled":"1","article_type":"original","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Orphan solute carrier (SLC) represents a group of membrane transporters whose exact functions and substrate specificities are not known. Elucidating the function and regulation of orphan SLC transporters is not only crucial for advancing our knowledge of cellular and molecular biology but can potentially lead to the development of new therapeutic strategies. Here, we provide evidence for the biological function of a ubiquitous orphan lysosomal SLC, the Major Facilitator Superfamily Domain-containing Protein 1 (MFSD1), which has remained phylogenetically unassigned. Targeted metabolomics revealed that dipeptides containing either lysine or arginine residues accumulate in lysosomes of cells lacking MFSD1. Whole-cell patch-clamp electrophysiological recordings of HEK293-cells expressing MFSD1 on the cell surface displayed transport affinities for positively charged dipeptides in the lower mM range, while dipeptides that carry a negative net charge were not transported. This was also true for single amino acids and tripeptides, which MFSD1 failed to transport. Our results identify MFSD1 as a highly selective lysosomal lysine/arginine/histidine-containing dipeptide exporter, which functions as a uniporter."}],"department":[{"_id":"DaSi"}],"acknowledged_ssus":[{"_id":"Bio"}],"date_created":"2024-03-31T22:01:12Z","issue":"13","external_id":{"pmid":["38507452"]},"type":"journal_article","acknowledgement":"We thank the Metabolomics Facility at Vienna BioCenter Core Facilities, which is a member of the Vienna BioCenter and funded by the City of Vienna through the Vienna Business Agency (shared research facility), for the LC–MS/MS analysis; and the BioImaging Facility at IST Austria for technical support and assistance. The authors want to thank N. Kastner for help with the live  cell  imaging  and  A.  Korošec  for  help  with  flow  cytometry.  This  work  was  supported by the Austrian Science Fund (FWF), grant P 36621- B (to M.R.), grant P 36667 (to W.S.), and core funding from IST Austria (to D.S.).","oa":1,"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"},"article_number":"e2319686121","doi":"10.1073/pnas.2319686121","status":"public","file":[{"file_size":2483787,"date_created":"2024-04-02T08:54:28Z","success":1,"file_name":"2024_PNAS_Boytsov.pdf","content_type":"application/pdf","creator":"dernst","file_id":"15256","date_updated":"2024-04-02T08:54:28Z","access_level":"open_access","relation":"main_file","checksum":"06f9e60b1146a685d58bf33999422fa8"}],"year":"2024","date_updated":"2024-04-02T08:58:40Z","article_processing_charge":"Yes (in subscription journal)","day":"26","has_accepted_license":"1","file_date_updated":"2024-04-02T08:54:28Z","date_published":"2024-03-26T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}