Abstract
The study of mitochondrial physiology continues to provide new and surprising insights into how this organelle participates in the integration of cellular activities, far beyond the traditional view of the mitochondrion in energy transduction. Emerging evidence indicates that mitochondria are a centre of organization of numerous signalling pathways and are a cellular target that undergoes vast modification during both the acute and chronic phases of disease development and ageing. In this context, it is also important to understand the spatial and temporal organization of mitochondrial function and how this might influence the cell's response to stress. Here, we present evidence supporting the hypothesis that mitochondria from heart cells act as a network of coupled oscillators, capable of producing frequency- and/or amplitude-encoded reactive oxygen species (ROS) signals under physiological conditions. This intrinsic property of the mitochondria can lead to a mitochondrial 'critical' state, i.e. an emergent macroscopic response manifested as complete collapse or synchronized oscillation in the mitochondrial network under stress. The large amplitude depolarizations of ΔΨm and bursts of ROS have widespread effects on all subsystems of the cell including energy-sensitive ion channels in the plasma membrane, producing an effect that scales to cause organ level electrical and contractile dysfunction. Mitochondrial ion channels appear to play a key role in the mechanism of this non-linear network phenomenon and hence are an important target for potential therapeutic intervention.
Original language | English (US) |
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Title of host publication | Mitochondrial Biology |
Subtitle of host publication | New Perspectives |
Publisher | wiley |
Pages | 140-151 |
Number of pages | 12 |
ISBN (Electronic) | 9780470725207 |
ISBN (Print) | 9780470066577 |
DOIs | |
State | Published - May 20 2008 |
Keywords
- Inner membrane anion channel
- Mitochondrial criticality
- Mitochondrial ion channels
- Mitochondrial oxidative phosphorylation
- Physiological and pathophysiological behaviour
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology