From mitochondrial dynamics to arrhythmias

M. A. Aon, S. Cortassa, F. G. Akar, D. A. Brown, L. Zhou, B. O'Rourke

Research output: Contribution to journalReview articlepeer-review

Abstract

The reactive oxygen species (ROS)-dependent mitochondrial oscillator described in cardiac cells exhibits at least two modes of function under physiological conditions or in response to metabolic and oxidative stress. Both modes depend upon network behavior of mitochondria. Under physiological conditions cardiac mitochondria behave as a network of coupled oscillators with a broad range of frequencies. ROS weakly couples mitochondria under normal conditions but becomes a strong coupling messenger when, under oxidative stress, the mitochondrial network attains criticality. Mitochondrial criticality is achieved when a threshold of ROS is overcome and a certain density of mitochondria forms a cluster that spans the whole cell. Under these conditions, the slightest perturbation triggers a cell-wide collapse of the mitochondrial membrane potential, Δψm, visualized as a depolarization wave throughout the cell which is followed by whole cell synchronized oscillations in Δψm, NADH, ROS, and GSH. This dynamic behavior scales from the mitochondrion to the cell by driving cellular excitability and the whole heart into catastrophic arrhythmias. A network collapse of Δψm under criticality leads to: (i) energetic failure, (ii) temporal and regional alterations in action potential (AP), (iii) development of zones of impaired conduction in the myocardium, and, ultimately, (iv) a fatal ventricular arrhythmia.

Original languageEnglish (US)
Pages (from-to)1940-1948
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume41
Issue number10
DOIs
StatePublished - Oct 2009

Keywords

  • Action potential
  • Inner membrane anion channel
  • Mitochondrial oscillations
  • Permeability transition
  • Reactive oxygen species
  • Redox potential
  • Sarcolemmal K channel

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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