PXD015873 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in maintaining mitochondrial metabolic homeostasis |
Description | The molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other. We show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline or an increase in OXPHOS. Our work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:03:48.611.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Lisa Jenkins |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-17 03:06:50 | ID requested | |
1 | 2020-01-16 01:55:35 | announced | |
⏵ 2 | 2024-10-22 04:03:49 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LC-MS, TRAP1,SILAC, HSP90 paralog |
Contact List
Lisa Jenkins |
contact affiliation | Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health |
contact email | lisa.jenkins@nih.gov |
lab head | |
Lisa Jenkins |
contact affiliation | National Cancer Institute, NIH |
contact email | lisa.jenkins@nih.gov |
dataset submitter | |
Full Dataset Link List
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://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD015873 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD015873
- Label: PRIDE project
- Name: The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in maintaining mitochondrial metabolic homeostasis