The effect of nitric oxide on mitochondrial respiration

Nitric Oxide. 2019 Jul 1:88:61-72. doi: 10.1016/j.niox.2019.04.005. Epub 2019 Apr 16.


This article reviews the interactions between nitric oxide (NO) and mitochondrial respiration. Mitochondrial ATP synthesis is responsible for virtually all energy production in mammals, and every other process in living organisms ultimately depends on that energy production. Furthermore, both necrosis and apoptosis, that summarize the main forms of cell death, are intimately linked to mitochondrial integrity. Endogenous and exogenous •NO inhibits mitochondrial respiration by different well-studied mechanisms and several nitrogen derivatives. Instantaneously, low concentrations of •NO, specifically and reversibly inhibit cytochrome c oxidase in competition with oxygen, in several tissues and cells in culture. Higher concentrations of •NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain, uncoupling, permeability transition, and/or cell death. Peroxynitrite can cause opening of the permeability transition pore and opening of this pore causes loss of cytochrome c, which in turn might contribute to peroxynitrite-induced inhibition of respiration. Therefore, the inhibition of cytochrome c oxidase by •NO may be involved in the physiological and/or pathological regulation of respiration rate, and its affinity for oxygen, which depend on reactive nitrogen species formation, pH, proton motriz force and oxygen supply to tissues.

Keywords: Cellular respiration; Cytochrome c oxidase; Mitochondria; Nitric oxide.

Publication types

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

MeSH terms

  • Animals
  • Bacteria
  • Cell Respiration / physiology*
  • Electron Transport Complex IV / antagonists & inhibitors
  • Humans
  • Mitochondria / metabolism*
  • Nitric Oxide / physiology*
  • Peroxynitrous Acid / physiology
  • Plants


  • Peroxynitrous Acid
  • Nitric Oxide
  • Electron Transport Complex IV