Mitochondrial ROS-induced ROS release: An update and review

Dmitry B. Zorov, Magdalena Juhaszova, Steven J. Sollott

Research output: Contribution to journalArticlepeer-review

747 Scopus citations


Unstable mitochondrial membrane potential and redox transitions can occur following insults including ischemia/reperfusion injury and toxin exposure, with negative consequences for mitochondrial integrity and cellular survival. These transitions can involve mechanisms such as the recently described process, "Reactive Oxygen Species (ROS)-induced ROS-release" (RIRR), and be generated by circuits where the mitochondrial permeability transition (MPT) pore and the inner membrane anion channel (IMAC) are involved. The exposure to excessive oxidative stress results in an increase in ROS reaching a threshold level that triggers the opening of one of the requisite mitochondrial channels. In turn, this leads to the simultaneous collapse of the mitochondrial membrane potential and a transient increased ROS generation by the electron transfer chain. Generated ROS can be released into cytosol and trigger RIRR in neighboring mitochondria. This mitochondrion-to-mitochondrion ROS-signaling constitutes a positive feedback mechanism for enhanced ROS production leading to potentially significant mitochondrial and cellular injury. This review and update considers a variety of RIRR mechanisms (involving MPT, IMAC and episodes of mitochondrial transient hyperpolarization). RIRR could be a general cell biology phenomenon relevant to the processes of programmed mitochondrial destruction and cell death, and may contribute to other mechanisms of post-ischemic pathologies, including arrhythmias.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalBiochimica et Biophysica Acta - Bioenergetics
Issue number5-6
StatePublished - May 2006
Externally publishedYes


  • Cardiac myocytes
  • Membrane potential
  • Oscillation
  • Oxidative stress
  • Permeability transition pore
  • Redox

ASJC Scopus subject areas

  • Biophysics


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