2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction
Kaul H, Isermann L, Senft K, Popovic M, Georgomanolis T, Baumann L, Sivanesan P, Pouikli A, Nolte H, Lucic B, Hildebrandt X, Seidel K, Gnad T, Gaedke F, Göbel U, Peters F, Cherevatenko M, Park J, Schauss A, Peltzer N, Brüning J, Kornfeld J, Pfeifer A, Langer T, Lusic M, Wickström S, Frezza C, Trifunovic A. 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction. Nature Metabolism 2025, 7: 1593-1613. PMID: 40750944, PMCID: PMC12373511, DOI: 10.1038/s42255-025-01332-8.Peer-Reviewed Original ResearchConceptsBrown adipose tissueNuclear stiffnessResponse to mitochondrial dysfunctionMitochondrial dysfunctionLipid droplet enlargementD-2HGAccumulation of lipid dropletsProtease ClpPFatty acid oxidationBrown adipocytesCellular homeostasisEpigenetic signaturesCellular metabolismGene expressionOncometabolite D-2-hydroxyglutarateD-2-hydroxyglutarateLipid dropletsMolecular underpinningsLipid accumulationExtrinsic cuesNuclear softeningAcid oxidationAdipose tissueClpPMitochondria
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