Role of the Mitochondrial Permeability Transition in Myocardial Disease

ABSTRACT—Mitochondria play a key role in determining cell fate during exposure to stress. Their role during ischemia/reperfusion is particularly critical because of the conditions that promote both apoptosis by the mitochondrial pathway and necrosis by irreversible damage to mitochondria in associat...

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Bibliographic Details
Published in:Circulation research 2003-08, Vol.93 (4), p.292-301
Main Authors: Weiss, James N, Korge, Paavo, Honda, Henry M, Ping, Peipei
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium - metabolism
Cardiology. Vascular system
Cardiomyopathies - metabolism
Cardiomyopathies - physiopathology
Coronary heart disease
Cytochrome c Group - secretion
Heart
Humans
Intracellular Membranes - physiology
Medical sciences
Mitochondria, Heart - physiology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - physiopathology
Permeability
Reactive Oxygen Species - metabolism
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Summary:ABSTRACT—Mitochondria play a key role in determining cell fate during exposure to stress. Their role during ischemia/reperfusion is particularly critical because of the conditions that promote both apoptosis by the mitochondrial pathway and necrosis by irreversible damage to mitochondria in association with mitochondrial permeability transition (MPT). MPT is caused by the opening of permeability transition pores in the inner mitochondrial membrane, leading to matrix swelling, outer membrane rupture, release of apoptotic signaling molecules such as cytochrome c from the intermembrane space, and irreversible injury to the mitochondria. During ischemia (the MPT priming phase), factors such as intracellular Ca accumulation, long-chain fatty acid accumulation, and reactive oxygen species progressively increase mitochondrial susceptibility to MPT, increasing the likelihood that MPT will occur on reperfusion (the MPT trigger phase). Because functional cardiac recovery ultimately depends on mitochondrial recovery, cardioprotection by ischemic and pharmacological preconditioning must ultimately involve the prevention of MPT. Investigations into this area are beginning to unravel some of the mechanistic links between cardioprotective signaling and mitochondria.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000087542.26971.D4