Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL005102-09
Application #
8746588
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2013
Total Cost
$508,015
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
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; 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
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

Showing the most recent 10 out of 36 publications