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The Central Role of the Mitochondria

Newer data indicate that the mitochondria are pivotal for several aspects of melatonin: its production, metabolism, and activity through receptors (1). Rather than respond to the signals of the light/dark cycle or the pineal gland, the mitochondria can induce the production of melatonin based on intracellular need. Levels of melatonin are known to be higher in mitochondria compared with blood levels, most likely due to the greater antioxidant requirements with the copious amounts of free radicals generated through the electron transport chain (2). Melatonin assists in mitochondrial redox balance through its ability to reduce the superoxide anion molecule from the electron transport chain and to directly scavenge free radicals (3). In addition to these functions, melatonin facilitates mitochondrial function by encouraging healthy endogenous levels of antioxidant defense enzymes like superoxide dismutase.


Mitochondrial dysfunction is one of the mechanisms related to diseases of aging (3). It may be that declining melatonin levels with age and, thus, less protection of the mitochondria from oxidative stress may be contributors to preclinical changes and, ultimately clinical symptoms. There may be the ability to offset some of the decline accompanying the aging process through physiological regeneration with supplemental melatonin, as has been documented in animal and human studies (3).



Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame

Reviewer: Peer-review in Nutrients Journal

Last updated: September 22, 2022



1. Tan DX, Reiter RusselJ. Mitochondria: the birth place, battle ground and the site of melatonin metabolism in cells. Melatonin Research. 2019;2(1).

2. Tan DX, Manchester LC, Esteban-Zubero E, Zhou Z, Reiter RJ. Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules. 2015.

3. Reiter R, Tan D, Rosales-Corral S, Galano A, Zhou X, Xu B. Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions. Molecules. 2018 Feb 24;23(2):509.

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