⮝ Full datasets listing
PXD076639
PXD076639 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | HYPOXIA RESCUES COMPLEX 1-ASSOCIATED DISEASE CAUSED BY DEFECTS IN THE HTRA2-CLPB PROTEOSTASIS SYSTEM |
| Description | Impaired mitochondrial proteostasis underlies a broad spectrum of diseases, yet effective therapies remain limited. Our prior CRISPR screens nominated more than 75 disease genes whose deficiency could be rescued by hypoxia therapy, including HTRA2, a mitochondrial intermembrane space protease. Here, we validated this concept in an Htra2 mutant mouse model that displays severe neurodegeneration and early lethality, closely mirroring human disease. Continuous hypoxia rescued striatal degeneration and extended lifespan. Mechanistically, we found that HTRA2 forms a functional complex with the disaggregase CLPB. Loss of either protein's function drives aggregation of intermembrane space-facing subunits of ETC Complex 1 (C1), resulting in secondary C1 dysfunction. This impairs tissue oxygen consumption and likely causes pathological hyperoxia, which is corrected by hypoxia. Together, these findings define a proteostasis pathway linking intermembrane space quality control to C1 function and expand the potential of hypoxia therapy to secondary C1 disease |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-05-29 |
| AnnouncementXML | Submission_2026-05-29_10:56:01.147.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Ankur Garg |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | unknown modification |
| Instrument | timsTOF HT |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-04-06 18:03:25 | ID requested | |
| ⏵ 1 | 2026-05-29 10:56:01 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: HTRA2, Hypoxia, Proteostasis, CLPB, Complex 1, DatasetType:Proteomics |
Contact List
| Isha Jain | |
|---|---|
| contact affiliation | Gladstone Institutes |
| contact email | isha.jain@gladstone.ucsf.edu |
| lab head | |
| Ankur Garg | |
| contact affiliation | UCSF |
| contact email | ankur.garg@ucsf.edu |
| 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/v12/MSV000101385/ |
