Abstract

The Role of Mitochondrial Homeostasis and Molecular Regulation of Mitochondrial Biogenesis in the Heart: Current data suggest that mitochondria may play a central role in the promotion of cell survival across multiple cell/tissue types. In the heart (and other organs) a phenomenon named preconditioning seems to activate the cell survival response conferring enhanced tolerance towards ischemic insults. We and others have begun to demonstrate that the mitochondria may be central to the preconditioning phenomenon. This biological phenomenon is being exploited to enhance our understanding of the molecular regulation of mitochondrial function to promote myocardial cell survival in the heart as a putative adaptive modulation in heart failure and in ischemic heart disease. Here we focus on the regulatory control of mitochondrial biogenesis, as a putative adaptive program that could be manipulated to augment cardiac tolerance to ischemia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005102-04
Application #
7735017
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2008
Total Cost
$423,042
Indirect Cost

  Institution

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

  Publications

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
Sack, Michael N (2013) Obesity and Cardiac Function - The Role of Caloric Excess and its Reversal. Drug Discov Today Dis Mech 10:e41-e46
Lynn, Edward G; McLeod, Christopher J; Gordon, Jeffrey P et al. (2008) SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells. FEBS Lett 582:2857-62
Minners, Jan; Lacerda, Lydia; Yellon, Derek M et al. (2007) Diazoxide-induced respiratory inhibition - a putative mitochondrial K(ATP) channel independent mechanism of pharmacological preconditioning. Mol Cell Biochem 294:11-8
True, Andrea L; Olive, Michelle; Boehm, Manfred et al. (2007) Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide. Circ Res 101:893-901
Lynn, Edward G; Lu, Zhongping; Minerbi, Diane et al. (2007) The regulation, control, and consequences of mitochondrial oxygen utilization and disposition in the heart and skeletal muscle during hypoxia. Antioxid Redox Signal 9:1353-61
Shiva, Sruti; Sack, Michael N; Greer, James J et al. (2007) Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 204:2089-102
Sack, Michael N (2006) Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance. Cardiovasc Res 72:210-9
Sack, Michael N (2006) Exploring mitochondria in the intact ischemic heart: advancing technologies to image intracellular function. Circulation 114:1452-4

Showing the most recent 10 out of 19 publications