Copyright © 2006, European Society of Cardiology
Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance
Cardiology Branch, NHLBI, National Institutes of Health, Building 10-CRC, Room 5-3150, 10 Center Drive, Bethesda, MD 20892-1454, USA
* Tel.: +1 301 402 9259; fax: +1 301 402 0888. Email address: sackm{at}nhlbi.nih.gov
Modest depolarization of the mitochondrial inner membrane potential is known to attenuate mitochondrial reactive oxygen species generation. Transient pharmacologic uncoupling of mitochondrial oxidative phosphorylation results in modest depolarization of the mitochondrial membrane potential and confers protection against subsequent cardiac ischemia–reperfusion injury. Whether cardiac mitochondria have an innate capacity to temporally self-modulate their membrane potential as a possible adaptive mechanism in the context of cardiac ischemia and early reperfusion is supported by emerging data and is an intriguing concept that warrants further investigation. The objective of this review is to explore the various mechanisms whereby mitochondrial depolarization can be evoked in the context of both cardiac ischemia and reperfusion and in response to the cardioprotective program of ischemic preconditioning. The potential regulatory pathways orchestrating this biological perturbation of mitochondrial function are explored from the level of signal transduction to potential transcription-mediated modulations of nuclear-encoded mitochondrial inner membrane proteins, emphasizing the potential function of the mitochondrial uncoupling proteins.
KEYWORDS Cardiac ischemia; Mitochondrial respiration; Uncoupling proteins; Reactive oxygen species; Mitochondrial depolarization
Time for primary review 26 days
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
Z. Lu, I. Scott, B. R. Webster, and M. N. Sack The Emerging Characterization of Lysine Residue Deacetylation on the Modulation of Mitochondrial Function and Cardiovascular Biology Circ. Res., October 23, 2009; 105(9): 830 - 841. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Wang, L. Huang, M. Abdelrahim, Q. Cai, A. Truong, R. Bick, B. Poindexter, and D. Sheikh-Hamad Stanniocalcin-1 suppresses superoxide generation in macrophages through induction of mitochondrial UCP2 J. Leukoc. Biol., October 1, 2009; 86(4): 981 - 988. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Golomb, A. Nyska, and H. Schwalb Occult Cardiotoxicity--Toxic Effects on Cardiac Ischemic Tolerance Toxicol Pathol, August 1, 2009; 37(5): 572 - 593. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kathiresan, M. Harvey, S. Orchard, Y. Sakai, and B. Sokolowski A Protein Interaction Network for the Large Conductance Ca2+-activated K+ Channel in the Mouse Cochlea Mol. Cell. Proteomics, August 1, 2009; 8(8): 1972 - 1987. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Heusch, K. Boengler, and R. Schulz Cardioprotection: Nitric Oxide, Protein Kinases, and Mitochondria Circulation, November 4, 2008; 118(19): 1915 - 1919. [Full Text] [PDF] |
||||
![]() |
Z. Lu and M. N. Sack ATF-1 Is a Hypoxia-responsive Transcriptional Activator of Skeletal Muscle Mitochondrial-uncoupling Protein 3 J. Biol. Chem., August 22, 2008; 283(34): 23410 - 23418. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Shiva, M. N. Sack, J. J. Greer, M. Duranski, L. A. Ringwood, L. Burwell, X. Wang, P. H. MacArthur, A. Shoja, N. Raghavachari, et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J. Exp. Med., September 3, 2007; 204(9): 2089 - 2102. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Westberg, M. Serlachius, P. Lankila, and L. C. Andersson Hypoxic preconditioning induces elevated expression of stanniocalcin-1 in the heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1766 - H1771. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Bodyak, D. L. Rigor, Y.-S. Chen, Y. Han, E. Bisping, W. T. Pu, and P. M. Kang Uncoupling protein 2 modulates cell viability in adult rat cardiomyocytes Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H829 - H835. [Abstract] [Full Text] [PDF] |
||||









