Mitochondrial criticality: A new concept at the turning point of life or death

Miguel Antonio Aon, Sonia Cortassa, Fadi Gabriel Akar, Brian O'Rourke

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)232-240
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1762
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Arrhythmias
  • Inner membrane anion channel
  • Ischemia-reperfusion injury
  • Mitochondrial oscillation
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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