TY - JOUR
T1 - Mitochondrial criticality
T2 - A new concept at the turning point of life or death
AU - Aon, Miguel Antonio
AU - Cortassa, Sonia
AU - Akar, Fadi Gabriel
AU - O'Rourke, Brian
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health: NIH R01 HL54598 (B.O'R.).
PY - 2006/2
Y1 - 2006/2
N2 - A variety of stressors can cause the collapse of mitochondrial membrane potential (ΔΨm), but the events leading up to this catastrophic cellular event are not well understood at the mechanistic level. Based on our recent studies of oscillations in mitochondrial energetics, we have coined the term "mitochondrial criticality" to describe the state in which the mitochondrial network of cardiomyocytes becomes very sensitive to small perturbations in reactive oxygen species (ROS), resulting in the scaling of local mitochondrial uncoupling and ΔΨm loss to the whole cell, and the myocardial syncytium. At the point of criticality, the dynamics of the mitochondrial network bifurcate to oscillatory behavior. These energetic changes are translated into effects on the electrical excitability of the cell, inducing dramatic changes in the morphology and the threshold for activating an action potential. Emerging evidence suggests that this mechanism, by creating spatial and temporal heterogeneity of excitability in the heart during ischemia and reperfusion, underlies the genesis of potentially lethal cardiac arrhythmias.
AB - A variety of stressors can cause the collapse of mitochondrial membrane potential (ΔΨm), but the events leading up to this catastrophic cellular event are not well understood at the mechanistic level. Based on our recent studies of oscillations in mitochondrial energetics, we have coined the term "mitochondrial criticality" to describe the state in which the mitochondrial network of cardiomyocytes becomes very sensitive to small perturbations in reactive oxygen species (ROS), resulting in the scaling of local mitochondrial uncoupling and ΔΨm loss to the whole cell, and the myocardial syncytium. At the point of criticality, the dynamics of the mitochondrial network bifurcate to oscillatory behavior. These energetic changes are translated into effects on the electrical excitability of the cell, inducing dramatic changes in the morphology and the threshold for activating an action potential. Emerging evidence suggests that this mechanism, by creating spatial and temporal heterogeneity of excitability in the heart during ischemia and reperfusion, underlies the genesis of potentially lethal cardiac arrhythmias.
KW - Arrhythmias
KW - Inner membrane anion channel
KW - Ischemia-reperfusion injury
KW - Mitochondrial oscillation
KW - Oxidative stress
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U2 - 10.1016/j.bbadis.2005.06.008
DO - 10.1016/j.bbadis.2005.06.008
M3 - Review article
C2 - 16242921
AN - SCOPUS:29344465712
VL - 1762
SP - 232
EP - 240
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 2
ER -