, Volume 27, Issue 2, pp 159–168 | Cite as

Melatonin and nitric oxide

Two required antagonists for mitochondrial homeostasis
  • Darío Acuña-Castroviejo
  • Germaine Escames
  • Luis C. López
  • Ana B. Hitos
  • Josefa León


The presence of nitric oxide (NO·) in the mitochondria led to analysis of its source and functions in mitochondrial homeostasis. Studies have revealed the existence of a mtNOS isoform with similar features to nNOS, with some post-traslational modifications, although without the typical signal peptide responsible for addressing proteins to mitochondrion. This isoform may account for the physiological production of NO· related to the respiratory control. During inflammatory conditions there is an excess of NO· in the mitochondria responsible for an increase in reactive oxygen and nitrogen species in sufficient amounts to compromise mitochondrial function. These conditions led to the discovery of the presence of an inducible mtNOS isoform with kinetic properties similar to iNOS. Experiments with knockout mice lacking either nNOS or iNOS further confirmed the existence of these two mtNOS isoforms in mitochondria. Although the increase in NO· in sepsis by inducible mtNOS may have important regulatory functions including the redistribution of oxygen into other pathways under hypoxia, it causes the production of excess NO· that is deleterious for the cell. Melatonin, an endogenous antioxidant, regulates mitochondrial respiration and bioenergetics and protects mitochondria from excess NO· by controlling the activity of mtNOS.

Key Words

Melatonin nitric oxide mitochondrial nitric oxide synthase mitochondria respiratory chain ATP oxidative stress sepsis 


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Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Darío Acuña-Castroviejo
    • 1
  • Germaine Escames
    • 1
  • Luis C. López
    • 1
  • Ana B. Hitos
    • 1
  • Josefa León
    • 1
  1. 1.Departmento de Fisiología, Instituto de BiotecnologíaUniversided de GranadaGranadaSpain

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