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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Project End
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Budget End
Support Year
8
Fiscal Year
2012
Total Cost
$829,255
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Type
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Traba, Javier; Sack, Michael N (2016) The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome. Cell Mol Life Sci :
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
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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

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