PXD022137 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Oncometabolism Drives Autophagy Activation in Skeletal Muscle |
Description | Metabolic rewiring is a well-established feature of muscle cells and a hallmark of cancer. In isocitrate dehydrogenase 1 and 2 mutant tumors, increased production of the oncometabolite D-2-hydroxyglutarate (D2-HG) is associated with myopathy. The connection between metabolic changes and proteomic remodeling in skeletal muscle remains poorly understood. We demonstrate that D2-HG impairs NAD+ redox homeostasis in myocytes, causing activation of autophagy via de-acetylation of microtubule-associated protein 1 light chain 3-II (LC3-II) by the nuclear deacetylase Sirt1. We integrated multi-omics data from mice treated with D2-HG and demonstrate that autophagy activation leads to skeletal muscle atrophy and sex-dependent metabolic and proteomic remodeling. We also characterized protein and metabolite interactions linking energy-substrate metabolism with chromatin organization and autophagy regulation. Collectively, our multi-omics approach exposes mechanisms by which the oncometabolite D2-HG induces metabolic and proteomic remodeling in skeletal muscle, and provides a conceptual framework for identifying potential therapeutic targets in cachexia. |
HostingRepository | PRIDE |
AnnounceDate | 2024-08-11 |
AnnouncementXML | Submission_2024-08-10_16:53:01.942.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Vidya Venkatraman |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-22 15:30:17 | ID requested | |
⏵ 1 | 2024-08-10 16:53:02 | announced | |
Publication List
Gao Y, Kim K, Vitrac H, Salazar RL, Gould BD, Soedkamp D, Spivia W, Raedschelders K, Dinh AQ, Guzman AG, Tan L, Azinas S, Taylor DJR, Schiffer W, McNavish D, Burks HB, Gottlieb RA, Lorenzi PL, Hanson BM, Van Eyk JE, Taegtmeyer H, Karlstaedt A, Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG. Mol Metab, 86():101969(2024) [pubmed] |
10.1016/j.molmet.2024.101969; |
Keyword List
submitter keyword: Autophagy,Mouse, Cancer, Cachexia, D2-HG, Skeletal Muscle |
Contact List
Dr. Jennifer Van Eyk |
contact affiliation | Director, Advanced Clinical Biosystems Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 |
contact email | jennifer.vaneyk@cshs.org |
lab head | |
Vidya Venkatraman |
contact affiliation | Cedar-Sinai Medical Center |
contact email | vidya.venkatraman@cshs.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022137
- Label: PRIDE project
- Name: Oncometabolism Drives Autophagy Activation in Skeletal Muscle