Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation. Mol Cell 2019 May 16;74(4):844-857.e7
Date
04/20/2019Pubmed ID
31000437Pubmed Central ID
PMC6525068DOI
10.1016/j.molcel.2019.03.021Scopus ID
2-s2.0-85065617020 (requires institutional sign-in at Scopus site) 112 CitationsAbstract
Brown adipose tissue (BAT) is rich in mitochondria and plays important roles in energy expenditure, thermogenesis, and glucose homeostasis. We find that levels of mitochondrial protein succinylation and malonylation are high in BAT and subject to physiological and genetic regulation. BAT-specific deletion of Sirt5, a mitochondrial desuccinylase and demalonylase, results in dramatic increases in global protein succinylation and malonylation. Mass spectrometry-based quantification of succinylation reveals that Sirt5 regulates the key thermogenic protein in BAT, UCP1. Mutation of the two succinylated lysines in UCP1 to acyl-mimetic glutamine and glutamic acid significantly decreases its stability and activity. The reduced function of UCP1 and other proteins in Sirt5KO BAT results in impaired mitochondria respiration, defective mitophagy, and metabolic inflexibility. Thus, succinylation of UCP1 and other mitochondrial proteins plays an important role in BAT and in regulation of energy homeostasis.
Author List
Wang G, Meyer JG, Cai W, Softic S, Li ME, Verdin E, Newgard C, Schilling B, Kahn CRMESH terms used to index this publication - Major topics in bold
Adipose Tissue, BrownAnimals
Energy Metabolism
Gene Expression Regulation
Glucose
Mice
Mice, Knockout
Mitochondria
Mitochondrial Proteins
Obesity
Proteomics
Sirtuins
Succinic Acid
Thermogenesis
Uncoupling Protein 1