PXD049093-1

PXD049093 is an original dataset announced via ProteomeXchange.

Title	Mouse adipocytes ex vivo from obese Rbm43 knockout mice
Description	Obesity is associated with systemic inflammation that impairs mitochondrial function. These changes curtail oxidative metabolism, limiting adipocyte lipid metabolism and thermogenesis, a metabolically beneficial program that dissipates chemical energy as heat. Here, we show that PGC1⍺, a key governor of mitochondrial biogenesis, is negatively regulated at the level of its mRNA translation by the RNA-binding protein RBM43. RBM43 is induced by inflammatory cytokines and suppresses mitochondrial biogenesis in a PGC1⍺-dependent manner. In mice, adipocyte-selective Rbm43 disruption elevates PGC1⍺ translation and oxidative metabolism. In obesity, Rbm43 loss confers body weight-independent protection from glucose intolerance, adipose inflammation, and activation of the innate immune sensor cGAS-STING. We further identify a role for PGC1⍺ in safeguarding against cytoplasmic accumulation of mitochondrial DNA, a cGAS ligand. The action of RBM43 defines a translational regulatory pathway by which inflammatory signals dictate cellular energy metabolism and contribute to metabolic disease pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2025-01-10
AnnouncementXML	Submission_2025-01-10_13:53:39.993.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Dumesic
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-01 18:00:56	ID requested
⏵ 1	2025-01-10 13:53:40	announced

Dataset with its publication pending

submitter keyword: mouse, proteomics, obesity, adipocytes, diabetes

Bruce Spiegelman
contact affiliation	Dana-Farber Cancer Institute and Harvard Medical School
contact email	bruce_spiegelman@dfci.harvard.edu
lab head
Phillip Dumesic
contact affiliation	Dana-Farber Cancer Institute
contact email	phillipA_dumesic@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD049093
     1. Label: PRIDE project
     2. Name: Mouse adipocytes ex vivo from obese Rbm43 knockout mice