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; Fyhrquist, Frej Y; Saijonmaa, Outi J et al. (2017) Basic Biology of Oxidative Stress and the Cardiovascular System: Part 1 of a 3-Part Series. J Am Coll Cardiol 70:196-211
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
Riley, Christopher L; Dao, Christine; Kenaston, M Alexander et al. (2016) The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation. J Physiol 594:7455-7464
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
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
Sack, Michael N (2013) Obesity and Cardiac Function - The Role of Caloric Excess and its Reversal. Drug Discov Today Dis Mech 10:e41-e46
Nguyen, Tiffany Tuyen M; Wong, Renee; Menazza, Sara et al. (2013) Cyclophilin D modulates mitochondrial acetylome. Circ Res 113:1308-19
Sack, Michael N (2012) The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging. J Mol Cell Cardiol 52:520-5

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