Protein targets modulated by SIRT3 are being explored using proteomic approaches. Characterization of the role of deacetylation of these targets will then be interogated, in a target function specific manner. We have recently identified a novel mitochondrial deacetylase and the targets fo this enzyme and its role in counterregulaing sirtuin funciton is being explored. Finally, we hyopothesized that acetylation of mitochondrial lysine residues will inhibit binding of xenobiotics metabolites to lysine residues and thereby modulate the mitochondrial catabolism of these potential toxic compounds. In light of the role acetaminophen plays in hepatic injury, we have initially explored this compound and find that the acetylation status of mitochondrial proteins does modulate susceptability to acetaminophen induced liver injury. This finding could have widespread implications in the prevention of hepatotoxicity and may have broader implications for other xenobiotics.

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National Heart, Lung, and Blood Institute
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Wu, Kaiyuan; Wang, Lingdi; Chen, Yong et al. (2018) GCN5L1 interacts with ?TAT1 and RanBP2 to regulate hepatic ?-tubulin acetylation and lysosome trafficking. J Cell Sci 131:
Thapa, Dharendra; Wu, Kaiyuan; Stoner, Michael W et al. (2018) The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial ?-oxidation enzyme HADHA. J Biol Chem 293:17676-17684
Scott, Iain; Wang, Lingdi; Wu, Kaiyuan et al. (2018) GCN5L1/BLOS1 Links Acetylation, Organelle Remodeling, and Metabolism. Trends Cell Biol 28:346-355
Wang, Lingdi; Scott, Iain; Zhu, Lu et al. (2017) GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis. Nat Commun 8:523
Traba, Javier; Sack, Michael N (2017) The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome. Cell Mol Life Sci 74:1777-1791
Traba, Javier; Geiger, Sarah S; Kwarteng-Siaw, Miriam et al. (2017) Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2. J Biol Chem 292:12153-12164
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

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