PXD022137-1

PXD022137 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-22 15:30:17	ID requested
⏵ 1	2024-08-10 16:53:02	announced

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;

submitter keyword: Autophagy,Mouse, Cancer, Cachexia, D2-HG, Skeletal Muscle

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

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/2024/08/PXD022137

PRIDE project URI

• PRIDE
  1. PXD022137
     1. Label: PRIDE project
     2. Name: Oncometabolism Drives Autophagy Activation in Skeletal Muscle