The Regulation of Mitochondrial Homeostasis and Fat Metabolism in Cardiac Pathology: Current data suggest that substrate metabolism and mitochondrial fitness may play a central role in cardiac adaptations to pathological stressors. In this project we are evaluating how proteins that control mitochondrial homeostasis and metabolism are both regulated and how they modulate cardiac pathology including pressure overload and cardiac ischemia. The candidate proteins being currently being explored include Park2 and Pink1, proteins that appear to be involved in fat metabolism and mitochondrial quality control programs. As human subjects have mutations in both Park2 and Pink1 skin fibroblast samples will be acquired to compare to the metabolic pathways perturned in murine models.

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National Heart, Lung, and Blood Institute
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Sack, Michael N (2018) Mitochondrial fidelity and metabolic agility control immune cell fate and function. J Clin Invest 128:3651-3661
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
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
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Traba, Javier; Kwarteng-Siaw, Miriam; Okoli, Tracy C et al. (2015) Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest 125:4592-600
Boylston, Jennifer A; Sun, Junhui; Chen, Yong et al. (2015) Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 88:73-81
Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary et al. (2014) Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res 103:485-97

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