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Regulation of mitochondrial functions by SIRT5 and non‐canonical post‐translational modifications (LB172)
Author(s) -
Lombard David,
Park Jeongsoon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb172
Subject(s) - succinylation , sirtuin , lysine , biochemistry , citric acid cycle , mitochondrion , chemistry , proteolysis , sirt2 , flux (metallurgy) , amino acid , pyruvate dehydrogenase complex , metabolism , biology , enzyme , nad+ kinase , organic chemistry
Protein function is regulated by diverse post‐translational modifications. The mitochondrial sirtuin SIRT5 removes malonyl and succinyl moieties from target lysines. The spectrum of protein substrates subject to these modifications is unknown. We recently reported the first systematic profiling of the mammalian succinylome, identifying 2565 succinylation sites on 779 proteins. Our analysis revealed potential impacts of lysine succinylation on amino acid degradation, the TCA cycle, and fatty acid metabolism. Lysine succinylation was also present on cytosolic and nuclear proteins; indeed, we found that a substantial fraction of SIRT5 was extra‐mitochondrial. SIRT5 repressed biochemical activity of, and cellular respiration through, two protein complexes identified in our analysis, Pyruvate Dehydrogenase Complex (PDC) and Succinate Dehydrogenase (SDH). We will discuss our recent progress on elucidating further the biology of SIRT5 using enzymatic, respiration, and metabolomic flux assays. Grant Funding Source : Supported by NIH awards R01GM101171 and R21CA177925 (D.L.).