Mitochondrial ion channels in cardiac function and dysfunction

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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 languageEnglish (US)
Title of host publicationMitochondrial Biology
Subtitle of host publicationNew Perspectives
Pages140-151
Number of pages12
StatePublished - Dec 1 2007

Publication series

NameNovartis Foundation Symposium
Volume287
ISSN (Print)1528-2511

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

O'Rourke, B., Cortassa, S., Akar, F., & Aon, M. (2007). Mitochondrial ion channels in cardiac function and dysfunction. In Mitochondrial Biology: New Perspectives (pp. 140-151). (Novartis Foundation Symposium; Vol. 287).