Melatonin in Mitochondria: Mitigating Clear and Present Dangers

Abstract

In cancer cells, glucose is primarily metabolized to pyruvate and then to lactate in the cytosol. By allowing the conversion of pyruvate to acetyl-CoA in mitochondria, melatonin reprograms glucose metabolism in cancer cells to a normal cell phenotype. Acetyl-CoA in the mitochondria also serves as a necessary co-factor for the rate-limiting enzyme in melatonin synthesis, thus ensuring melatonin production in mitochondria of normal cells.

Melatonin, coronavirus, cardiovascular disease, and the geriatric emergency: let's use everything we have!

“…Excellent reviews have noted that melatonin has significant beneficial effects against ischemia-reperfusion injury, myocardial chronic intermittent hypoxia injury, pulmonary hypertension, hypertension, valvular heart diseases, vascular diseases, and lipid metabolism. 3,4 Melatonin is synthesized from tryptophan in the pineal gland and by almost all the organs of the body, since its production is associated with mitochondria. It is noteworthy that high levels of melatonin play positive roles in health and aging.…”

“…It is noteworthy that high levels of melatonin play positive roles in health and aging. 3 Melatonin, a well-known chronobiotic, is also a promising adjunct drug for viral infections due to its anti-inflammatory, antiapoptotic, immunomodulatory, and powerful antioxidant properties. Melatonin binds to M1 and M2 receptors that can be found in the retinae and in the brain, as well as in the heart, gut, lymphocytes, and liver.…”

“…Melatonin binds to M1 and M2 receptors that can be found in the retinae and in the brain, as well as in the heart, gut, lymphocytes, and liver. 3 Melatonin levels change during the life span. Nocturnal melatonin levels are highest in young children, approximately 325 pg/mL and then decline gradually with age.…”

“…For example, levels are between 50 and 55pg/mL in 15 to 50-year-olds, approximately 27 pg/mL in 50 to 70-year-olds and approximately 15 pg/mL in persons > 70 years. 3 COVID-19 infection attacks the melatonin synthetic pathway resulting in reduced melatonin levels at a time when melatonin is most needed. This often leads to altered immune responses, specifically, with the overreaction of the innate immune response.…”

Transcriptomic Insights into the Effect of Melatonin in Saccharomyces cerevisiae in the Presence and Absence of Oxidative Stress

“…In humans, the action of melatonin is mitochondrion targeted, as the electron transport chain (ETC), where higher ROS production occurs, is located in the mitochondria [ 22 ]. Therefore, melatonin not only reduces ROS damage by scavenging ROS and increasing antioxidant enzyme activities but also improves the efficiency of the ETC and ATP production (reviewed in Reiter et al [ 23 ]). Zampol and Barros [ 24 ] revealed that the addition of melatonin to yeast cells improved respiration when the cells were challenged with a compound that induces oxidative stress (menadione), mainly by affecting complex IV activity, suggesting that melatonin may also exhibit mitochondrion-specific activity in yeast.…”