A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury

Cell Metab. 2016 Feb 9;23(2):254-63. doi: 10.1016/j.cmet.2015.12.009. Epub 2016 Jan 14.


Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted--ischemia--and then restored--reperfusion--leading to a burst of reactive oxygen species (ROS) from mitochondria. It has been tacitly assumed that ROS production during IR is a non-specific consequence of oxygen interacting with dysfunctional mitochondria upon reperfusion. Recently, this view has changed, suggesting that ROS production during IR occurs by a defined mechanism. Here we survey the metabolic factors underlying IR injury and propose a unifying mechanism for its causes that makes sense of the huge amount of disparate data in this area and provides testable hypotheses and new directions for therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Electron Transport
  • Humans
  • Mitochondria / metabolism*
  • Models, Biological
  • Reperfusion Injury / metabolism*
  • Sulfhydryl Compounds / metabolism
  • Superoxides / metabolism*


  • Sulfhydryl Compounds
  • Superoxides