⮝ Full datasets listing
PXD035605-1
PXD035605 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Loss of TMEM65 causes mitochondrial disease mediated by mitochondrial calcium |
| Description | Transmembrane protein 65 (TMEM65) depletion in a patient carrying a homozygous variant in the Tmem65 splice site resulted in severe mitochondrial encephalomyopathy, indicating the clinical importance of TMEM65. However, the function of TMEM65 remains unknown. Here, we generated a TMEM65 reporter mouse as well as whole-body and tissue-specific Tmem65 knockout (KO) mice to investigate the localization and function of TMEM65. We show that TMEM65 is localized to mitochondria in heart, skeletal muscle, and throughout the brain. Both whole-body and nervous system-specific Tmem65 KO result in severe growth retardation and sudden death following seizures ~3 weeks after birth, indicating TMEM65 is indispensable for normal brain function. In addition, we find that skeletal muscle-specific Tmem65 KO leads to progressive, adult-onset myopathy preceded by elevated mitochondrial calcium levels despite unaltered expression of known mitochondrial or cellular calcium handling proteins. Consistently, we demonstrate that ablation of TMEM65 results in a loss of sodium-dependent mitochondrial calcium export. Finally, we show that blocking mitochondrial calcium entry through removal of the mitochondrial calcium uniporter (MCU) rescues the early lethality of whole-body TMEM65 ablation. Our data not only reveal the essential role of TMEM65 in mammalian physiology, but also suggest modulating mitochondrial calcium may offer a potential therapeutical approach to address defects associated with TMEM65 misexpression. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-03-20 |
| AnnouncementXML | Submission_2026-03-20_08:51:59.550.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Angel Aponte |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2022-07-27 15:04:31 | ID requested | |
| ⏵ 1 | 2026-03-20 08:52:00 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: TMT, Mitochondria, Tmem65 |
Contact List
| Brian Glancy | |
|---|---|
| contact affiliation | NIH/NHLBI |
| contact email | Brian.Glancy@nih.gov |
| lab head | |
| Angel Aponte | |
| contact affiliation | NIH/NHLBI |
| contact email | apontea@nhlbi.nih.gov |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v04/MSV000089991/ |
