Melatonin mitigates mitochondrial meltdown: Interactions with SIRT3

Russel J. Reiter, Dun Xian Tan, Sergio Rosales-Corral, Annia Galano, Mei Jie Jou, Dario Acuna-Castroviejo

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations


Melatonin exhibits extraordinary diversity in terms of its functions and distribution. When discovered, it was thought to be uniquely of pineal gland origin. Subsequently, melatonin synthesis was identified in a variety of organs and recently it was shown to be produced in the mitochondria. Since mitochondria exist in every cell, with a few exceptions, it means that every vertebrate, invertebrate, and plant cell produces melatonin. The mitochondrial synthesis of melatonin is not photoperiod-dependent, but it may be inducible under conditions of stress. Mitochondria-produced melatonin is not released into the systemic circulation, but rather is used primarily in its cell of origin. Melatonin’s functions in the mitochondria are highly diverse, not unlike those of sirtuin 3 (SIRT3). SIRT3 is an NAD+-dependent deacetylase which regulates, among many functions, the redox state of the mitochondria. Recent data proves that melatonin and SIRT3 post-translationally collaborate in regulating free radical generation and removal from mitochondria. Since melatonin and SIRT3 have cohabitated in the mitochondria for many eons, we predict that these molecules interact in many other ways to control mitochondrial physiology. It is predicted that these mutual functions will be intensely investigated in the next decade and importantly, we assume that the findings will have significant applications for preventing/delaying some age-related diseases and aging itself.

Original languageEnglish (US)
Article number2439
JournalInternational journal of molecular sciences
Issue number8
StatePublished - Aug 18 2018
Externally publishedYes


  • Antioxidant enzymes
  • Molecular pathways
  • Oxidative phosphorylation
  • Oxidative stress
  • Reactive oxygen species
  • Sirtuins

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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