Melatonin Mitigates Mitochondrial Meltdown: Interactions with SIRT3

Abstract

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.

Melatonin: Roles in influenza, Covid‐19, and other viral infections

“…The evolutionary conserved relationship of melatonin-induced sirtuins is important to the maintenance of mitochondrial function, 40 highlighting another important aspect of normal mitochondrial function that viruses can disengage via the suppression of pineal and mitochondrial melatonin. to regulate dendritic cells, and therefore patterned immune activity.…”

Melatonin: Another avenue for treating osteoporosis?

“…In mammals, it is mainly secreted by the pineal gland during darkness, and exposure to light at night may decrease plasma melatonin levels . Apart from the pineal gland, studies have suggested that melatonin may be synthesized locally in the bone marrow as well as in many other tissues . Melatonin synthesized in the bone marrow can accumulate at concentrations twice that of nocturnal blood levels, which may produce strong local effects on bone.…”

“…16 Apart from the pineal gland, studies have suggested that melatonin may be synthesized locally in the bone marrow as well as in many other tissues. 17,18 Melatonin synthesized in the bone marrow can accumulate at concentrations twice that of nocturnal blood levels, 17,19,20 which may produce strong local effects on bone. Osteocytes exhibit a 24 hours cycle that is influenced by age, gender, diseases, and hormonal status.…”

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

“…This requires the disinhibition of the pyruvate dehydrogenase complex (PDC), with PDC driving the conversion of pyruvate to acetyl-CoA. As acetyl-CoA is also a necessary co-substate for AANAT and the activation of the mitochondrial melatoninergic pathway, circadian melatonin acts to upregulate mitochondrial melatonin and thereby increase levels of sirtuins and endogenous antioxidant enzymes, including superoxide dismutase (SOD)2 [88,89]. As such, local and circadian melatonin can significantly determine the changing immune responses required in placenta-regulating immune cells via impacts on mitochondrial function.…”