Abstract

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. In light of recent findings we have expanded this project into the clinical arena and are exploring the role of fasting and feeding in the modulation of the circulating inflammasome.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006047-07
Application #
9353120
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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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