PXD039061 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition |
Description | The intimate association between the endoplasmic reticulum (ER) and mitochondrial membranes at ER-mitochondria contact sites (ERMCS) serves as a platform for several critical cellular processes, particularly lipid synthesis. How contacts are remodeled and the subsequent biological consequences of altered contacts such as perturbed lipid metabolism remains poorly understood. Here we show that the p97 AAA-ATPase and its ER-tethered ubiquitin-X domain adaptor 8 (UBXD8) regulate the prevalence of ERMCS. The p97-UBXD8 complex localizes to contacts and its loss increases contacts in a manner that is dependent on p97 catalytic activity. Quantitative proteomics and lipidomics of ERMCS demonstrates alterations in proteins regulating lipid metabolism and a significant change in saturated or monounsaturated lipid species in UBXD8 knockout cells. We show that loss of p97-UBXD8 results in perturbed contacts due to an increase in membrane lipid saturation via SREBP1 and the lipid desaturase SCD1. These aberrant contacts can be rescued by supplementation with unsaturated fatty acids or overexpression of SCD1. Notably, we find that the SREBP1-SCD1 pathway is negatively impacted in the brains of mice with p97 mutations that cause neurodegeneration. Our results suggest that contacts are exquisitely sensitive to alterations to membrane lipid composition and saturation in a p97-UBXD8 dependent manner. |
HostingRepository | PRIDE |
AnnounceDate | 2023-01-25 |
AnnouncementXML | Submission_2023-01-25_09:23:21.490.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | JoaoPaulo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-22 02:24:47 | ID requested | |
⏵ 1 | 2023-01-25 09:23:21 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: SREBP1,ERMCS, SCD1, UBXD8, neurodegeneration |
Contact List
MalavikaRaman |
contact affiliation | Department of Developmental Molecular and Chemical Biology Tufts University School of Medicine Boston MA |
contact email | malavika.raman@tufts.edu |
lab head | |
JoaoPaulo |
contact affiliation | Harvard Medical School |
contact email | joao_paulo@post.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039061
- Label: PRIDE project
- Name: The p97-UBXD8 complex regulates ER-Mitochondria contact sites by altering membrane lipid saturation and composition