{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vetralla M"],"funding":["Telethon"],"pagination":["923"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12830682"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["The bidirectional transport of Ca<sup>2+</sup> into and out of mitochondria regulates metabolism, signaling, and cell fate. While influx is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, efflux mechanisms are more diversified, involving Na⁺ or H⁺ exchange pathways. We here demonstrate that TMEM65 is a fundamental component of the Ca<sup>2+</sup> efflux machinery of mitochondria. Its overexpression specifically enhances Na⁺- and Li⁺-dependent mitochondrial Ca²⁺ extrusion. This effect is inhibited by CGP-37157 and does not depends on NCLX, currently considered the bona fide mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchanger. Its downregulation chronically elevates basal [Ca²⁺]<sub>mt</sub> and impairs efflux upon stimulation. In Caenorhabditis elegans, deletion of TMEM65 "],"journal":["Nature communications"],"pubmed_title":["TMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis."],"pmcid":["PMC12830682"],"funding_grant_id":["GJC21054"],"pubmed_authors":["Ehninger D","De Stefani D","Habert MS","Kahsay A","Cadenelli V","Sbrissa M","Wischhof L","Scifo E","Rizzuto R","Bano D","Vetralla M","Xie B"],"additional_accession":[]},"is_claimable":false,"name":"TMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis.","description":"The bidirectional transport of Ca<sup>2+</sup> into and out of mitochondria regulates metabolism, signaling, and cell fate. While influx is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, efflux mechanisms are more diversified, involving Na⁺ or H⁺ exchange pathways. We here demonstrate that TMEM65 is a fundamental component of the Ca<sup>2+</sup> efflux machinery of mitochondria. Its overexpression specifically enhances Na⁺- and Li⁺-dependent mitochondrial Ca²⁺ extrusion. This effect is inhibited by CGP-37157 and does not depends on NCLX, currently considered the bona fide mitochondrial Na<sup>+</sup>/Ca<sup>2+</sup> exchanger. Its downregulation chronically elevates basal [Ca²⁺]<sub>mt</sub> and impairs efflux upon stimulation. In Caenorhabditis elegans, deletion of TMEM65 ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-13T05:08:07.346Z","creation":"2026-06-13T03:08:59.922Z"},"accession":"S-EPMC12830682","cross_references":{"pubmed":["41408045"],"doi":["10.1038/s41467-025-67647-y"]}}