title: Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart.
abstract: Studies to quantify the protein acetylome show that lysine-residue acetylation rivals phosphorylation in prevalence as a posttranslational modification. Interesting, this posttranslational modification is modified by nutrient flux and by redox stress and targets the vast majority of metabolic pathway proteins in the mitochondria. Furthermore, the mitochondrial deacetylase enzyme SIRT3 appears to be regulated by exercise in skeletal muscle and in response to pressure overload in the heart. The alteration of protein lysine residues by acetylation and the enzymes controlling deacetylation are beginning to be explored as important regulatory events in the control of mitochondrial function and homeostasis. This review focuses on the mitochondrial targets of SIRT3 that are functionally implicated in heart biology and pathology and on the direct cardiac consequences of the genetic manipulation of SIRT3. As therapeutic modulators of other SIRT isoforms have been identified, the longer-term objective of our understanding of this biology would be to identify SIRT3 modulators as putative cardiac therapeutic agents.
authors: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. sackm@nhlbi.nih.gov
authors: Michael N
authors: MN
authors: Sack
mesh_terms: D000107:Acetylation; D000818:Animals; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D004734:Energy Metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006331:Heart Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008239:Lysine; D008929:Mitochondria, Heart / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D017382:Reactive Oxygen Species; D056566:Sirtuin 3; D021983:Cyclophilins; D008239:Lysine