Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart.

Journal of Molecular and Cellular Cardiology
Alexander R LyonFadi G Akar

Abstract

Polarization of the mitochondrial membrane potential (DeltaPsi(m)) is critical for normal mitochondrial function and cellular energetics. Mitochondrial dysfunction, manifesting as disrupted DeltaPsi(m) polarization (i.e. depolarization or hyperpolarization), underlies several important and highly prevalent diseases, including a variety of cardiac and neurological disorders. As such, DeltaPsi(m) instability might form a unifying mechanism for a class of metabolic disorders affecting excitable tissues. Here, we measured the spatio-temporal kinetics of DeltaPsi(m) changes across the intact heart using high-resolution optical DeltaPsi(m) imaging and uncovered surprisingly complex spatial patterns and dynamically fluctuating changes in DeltaPsi(m) that developed into actively propagating waves of mitochondrial depolarization during global ischemia. Our data further indicated that the recovery of DeltaPsi(m) upon reperfusion is dictated by the duration of the preceding ischemic insult. Post-ischemic electrical and functional recovery was dependent on early DeltaPsi(m) recovery but independent of overall cellular injury measured using a standard assay of lactate dehydrogenase release. These findings reveal a novel mechanism by which i...Continue Reading

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Jun 8, 2014·Medical Hypotheses·Georgios BagkosChristina Piperi
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