Protein targets modulated by SIRT3 are being explored using proteomic approaches. Characterization of the role of deacetylation of these targets will then be interrogated, in a target function specific manner. We have recently identified a novel mitochondrial deacetylase and the targets of this enzyme and its role in counterregulating sirtuin function is being explored. We are now expanding our studies in this arena to explore the role of these nutrient sensing programs on mitochondrial quality control (mitophagy) and in the mitochondrial role in activating inflammatory pathways.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,261,198
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Murphy, Elizabeth; Ardehali, Hossein; Balaban, Robert S et al. (2016) Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association. Circ Res 118:1960-91
Lu, Zhongping; Chen, Yong; Aponte, Angel M et al. (2015) Prolonged fasting identifies heat shock protein 10 as a Sirtuin 3 substrate: elucidating a new mechanism linking mitochondrial protein acetylation to fatty acid oxidation enzyme folding and function. J Biol Chem 290:2466-76
Scott, Iain; Webster, Bradley R; Chan, Carmen K et al. (2014) GCN5-like protein 1 (GCN5L1) controls mitochondrial content through coordinated regulation of mitochondrial biogenesis and mitophagy. J Biol Chem 289:2864-72
Webster, Bradley R; Scott, Iain; Traba, Javier et al. (2014) Regulation of autophagy and mitophagy by nutrient availability and acetylation. Biochim Biophys Acta 1841:525-34
Webster, Bradley R; Scott, Iain; Han, Kim et al. (2013) Restricted mitochondrial protein acetylation initiates mitochondrial autophagy. J Cell Sci 126:4843-9
Webster, Bradley R; Lu, Zhongping; Sack, Michael N et al. (2012) The role of sirtuins in modulating redox stressors. Free Radic Biol Med 52:281-90
Avila, C; Huang, R J; Stevens, M V et al. (2012) Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins. Exp Clin Endocrinol Diabetes 120:248-51
Scott, Iain; Webster, Bradley R; Li, Jian H et al. (2012) Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1. Biochem J 443:655-61
Kim, Kye-Young; Sack, Michael N (2012) Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease. Curr Opin Lipidol 23:201-5
Sack, Michael N; Finkel, Toren (2012) Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb Perspect Biol 4:

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