The role of mitochondrial reactive oxygen species, NO and H2 S in ischaemia/reperfusion injury and cardioprotection

J Cell Mol Med. 2020 Jun;24(12):6510-6522. doi: 10.1111/jcmm.15279. Epub 2020 May 8.


Redox signalling in mitochondria plays an important role in myocardial ischaemia/reperfusion (I/R) injury and in cardioprotection. Reactive oxygen and nitrogen species (ROS/RNS) modify cellular structures and functions by means of covalent changes in proteins including among others S-nitros(yl)ation by nitric oxide (NO) and its derivatives, and S-sulphydration by hydrogen sulphide (H2 S). Many enzymes are involved in the mitochondrial formation and handling of ROS, NO and H2 S under physiological and pathological conditions. In particular, the balance between formation and removal of reactive species is impaired during I/R favouring their accumulation. Therefore, various interventions aimed at decreasing mitochondrial ROS accumulation have been developed and have shown cardioprotective effects in experimental settings. However, ROS, NO and H2 S play also a role in endogenous cardioprotection, as in the case of ischaemic pre-conditioning, so that preventing their increase might hamper self-defence mechanisms. The aim of the present review was to provide a critical analysis of formation and role of reactive species, NO and H2 S in mitochondria, with a special emphasis on mechanisms of injury and protection that determine the fate of hearts subjected to I/R. The elucidation of the signalling pathways of ROS, NO and H2 S is likely to reveal novel molecular targets for cardioprotection that could be modulated by pharmacological agents to prevent I/R injury.

Keywords: cardioprotection; heart; hydrogen sulphide; ischaemia; mitochondria; nitric oxide; reactive oxygen species; reperfusion.

Publication types

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

MeSH terms

  • Animals
  • Cardiotonic Agents / therapeutic use*
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Mitochondria, Heart / metabolism*
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / metabolism*
  • Nitric Oxide / metabolism*
  • Reactive Oxygen Species / metabolism*


  • Cardiotonic Agents
  • Reactive Oxygen Species
  • Nitric Oxide
  • Hydrogen Sulfide