Protective role of melatonin in mitochondrial dysfunction and related disorders

Arch Toxicol. 2015 Jun;89(6):923-39. doi: 10.1007/s00204-015-1475-z. Epub 2015 Feb 18.


Mitochondria are the powerhouse of the eukaryotic cell through their use of oxidative phosphorylation to generate ATP. Mitochondrial dysfunction is considered an important contributing factor in a variety of physiopathological situations such as aging, heart ischemia/reperfusion injury, diabetes and several neurodegenerative and cardiovascular diseases, as well as in cell death. Increased formation of reactive oxygen species, altered respiratory chain complexes activity and opening of the mitochondrial permeability transition pore have been suggested as possible factors responsible for impaired mitochondrial function. Therefore, preventing mitochondrial dysfunction could be an effective therapeutic strategy against cellular degenerative processes. Cardiolipin is a unique phospholipid located at the level of inner mitochondrial membrane where it plays an important role in mitochondrial bioenergetics, as well as in cell death. Cardiolipin abnormalities have been associated with mitochondrial dysfunction in a variety of pathological conditions and aging. Melatonin, the major secretory product of the pineal gland, is a well-known antioxidant agent and thus an effective protector of mitochondrial bioenergetic function. Melatonin was reported to prevent mitochondrial dysfunction from oxidative damage by preserving cardiolipin integrity, and this may explain, at least in part, the beneficial effect of this compound in mitochondrial physiopathology. In this article, mechanisms through which melatonin exerts its protective role in mitochondrial dysfunction and related disorders are reviewed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Cardiolipins / metabolism
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / physiopathology
  • Humans
  • Melatonin / administration & dosage
  • Melatonin / therapeutic use*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism


  • Antioxidants
  • Cardiolipins
  • Reactive Oxygen Species
  • Melatonin