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Confocal Imaging of Single Mitochondrial Superoxide Flashes in Intact Heart or In Vivo
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Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial

D B Zorov1, C R Filburn, L O Klotz

  • 1Laboratory of Cardiovascular Sciences, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA.

The Journal of Experimental Medicine
|October 4, 2000
PubMed

Insights

Reactive oxygen species (ROS) trigger mitochondrial permeability transition (MPT) in heart cells, leading to depolarization. This ROS-induced ROS release (RIRR) phenomenon suggests a fundamental link between ROS and MPT in mitochondria.

Area of Science:

  • Mitochondrial biology
  • Cellular redox signaling
  • Cardiomyocyte function

Background:

  • Mitochondria are key in cellular energy production and signaling.
  • Reactive oxygen species (ROS) are byproducts of metabolism with signaling roles.
  • Mitochondrial permeability transition (MPT) is a critical event in cell death pathways.

Purpose of the Study:

  • To investigate the direct relationship between ROS accumulation and MPT induction in cardiac myocytes.
  • To elucidate the role of ROS in triggering MPT and subsequent mitochondrial dysfunction.
  • To characterize the phenomenon of ROS-induced ROS release (RIRR) in the context of MPT.

Main Methods:

  • Development of a novel photoactivation model to induce incremental ROS accumulation in isolated cardiac myocytes.
  • Utilized tetramethylrhodamine derivatives for ROS generation and simultaneous monitoring of mitochondrial membrane potential (DeltaPsi).
  • Employed bongkrekic acid and calcein permeability assays to confirm MPT induction; used Trolox as a ROS scavenger.

Main Results:

  • Photodynamically induced ROS accumulation reproducibly triggered abrupt mitochondrial depolarization, indicative of MPT.
  • MPT induction was confirmed by bongkrekic acid's inhibitory effect and concurrent calcein permeability.
  • ROS-scavenging capacity, particularly glutathione, influenced the kinetics of MPT induction.
  • MPT induction was associated with a burst of mitochondrial ROS generation (RIRR).
  • MPT induction and RIRR were observed to occur synchronously and reversibly in adjacent mitochondria, suggesting cooperativity.

Conclusions:

  • Photodynamically generated ROS can directly induce MPT in cardiac myocytes.
  • The study establishes a direct link between MPT and ROS-induced ROS release (RIRR).
  • This MPT induction/RIRR phenomenon may represent a fundamental mechanism in mitochondrial and cellular physiology and pathology.

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