Document Detail


From mitochondrial dynamics to arrhythmias.
MedLine Citation:
PMID:  19703656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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, Delta psi(m), visualized as a depolarization wave throughout the cell which is followed by whole cell synchronized oscillations in Delta psi(m), 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 Delta psi(m) 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.
Authors:
M A Aon; S Cortassa; F G Akar; D A Brown; L Zhou; B O'Rourke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2009-03-05
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  41     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-08-25     Completed Date:  2009-11-04     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1940-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / etiology*,  metabolism*
Humans
Membrane Potential, Mitochondrial / physiology
Membrane Potentials / physiology
Mitochondria, Heart / metabolism,  physiology*
Oxidative Stress / physiology
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
P01 HL081427/HL/NHLBI NIH HHS; P01 HL081427-04/HL/NHLBI NIH HHS; P01-HL081427/HL/NHLBI NIH HHS; R00 HL095648/HL/NHLBI NIH HHS; R33 HL087338/HL/NHLBI NIH HHS; R33 HL087338-02/HL/NHLBI NIH HHS; R33-HL87345/HL/NHLBI NIH HHS; R37 HL054598/HL/NHLBI NIH HHS; R37 HL054598-13/HL/NHLBI NIH HHS; R37-HL54598/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species
Comments/Corrections

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