Melatonin, mitochondria, and cellular bioenergetics

Abstract

Aerobic cells use oxygen for the production of 90-95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four-electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production.

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion

“…These data agree with he interaction between melatonin and striatal D 1 /D 2 receptors elsewhere reported with electrophysiological approaches [18]. Experiments in vivo and in vitro have shown that melatonin promotes mitochondrial phosphorylation and ATP synthesis interacting with the electron transport chain complexes I and IV [5,[37][38][39]. These effects are related to the antioxidant role of melatonin, since it scavenges hydrogen peroxide [53] and increases mitochondrial GSH levels, counteracting the oxidative stress-induced mitochondrial damage [37].…”

“…These effects are related to the antioxidant role of melatonin, since it scavenges hydrogen peroxide [53] and increases mitochondrial GSH levels, counteracting the oxidative stress-induced mitochondrial damage [37]. These data, with those reporting an effect of melatonin on mitochondrial inner membrane fluidity [22], further support that mitochondria are an important target for melatonin action [2,5].…”

“…Melatonin is a strong scavenger of free radicals [46,48] and regulates the activity and expression of antioxidant enzymes [9,37]. Melatonin reportedly protects cells, tissues and organs against oxidative damage caused by various free radical generating agents [5,16,17]. Melatonin also protects the brain against oxidative damage [3,47].…”

“…In vitro, melatonin rescues DA neurons from MPP + -induced cell death [28], and protects mitochondrial dysfunction produced by the neurotoxin [1]. Recently, it was reported that melatonin protects mitochondria against oxidative stress, increasing the activity of complex I and IV and ATP production, and decreasing mitochondrial hydroperoxides [5,37,38].…”

A protective effect of melatonin on intestinal permeability is induced by diclofenac via regulation of mitochondrial function in mice

“…Melatonin also increased the production of ATP in control mitochondria. Acuña-Castroviejo et al documented that melatonin counteracted mitochondrial oxidative damage induced by t-butyl hydroperoxide, recovering glutathione levels and ATP production [45,46] . These data, along with other findings, suggest that melatonin regulates mitochondrial homeostasis [47] .…”