Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production

Abstract

The role of melatonin in improving mitochondrial respiratory chain activity and increasing ATP production in different experimental conditions has been widely reported. To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin on normal mitochondrial functions. Mitochondria were recovered from mouse liver cells and incubated in vitro with melatonin at concentrations ranging from 1 nm to 1 mm. Melatonin decreased oxygen consumption concomitantly with its concentration, inhibited any increase in oxygen flux in the presence of an excess of ADP, reduced the membrane potential, and consequently inhibited the production of superoxide anion and hydrogen peroxide. At the same time it maintained the efficiency of oxidative phosphorylation and ATP synthesis while increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles. Our results support the hypothesis that melatonin, together with hormones such as triiodothyronine, participates in the physiological regulation of mitochondrial homeostasis.

Efeito de diferentes concentrações de melatonina em espermatozoides de carneiros sobre estresse oxidativo após criopreservação

“…Tem sido relatado (Aitken & Clarkson 1987) que o axonema e as mitocôndrias na peça intermediária, podem ser danificados por níveis elevados de EROs. Estudos mostram que a melatonina pode estabilizar e proteger as mitocôndrias através de vários mecanismos (Martín et al 2000;Lopez et al 2009). Primeiro, as propriedades antioxidante e removedora de radicais livres da indoleamina protegem a organela dos danos oxidativos (Martín et al 2000).…”

“…Primeiro, as propriedades antioxidante e removedora de radicais livres da indoleamina protegem a organela dos danos oxidativos (Martín et al 2000). Segundo, a melatonina aumenta a atividade dos complexos respiratórios I, III e IV da cadeia de transporte de elétrons, reduzindo o fluxo de oxigênio e melhorando a eficiência respiratória das mitocôndrias (Lopez et al 2009) e aumentando a síntese de ATP em condições normais e estressantes (Acuna-Castroviejo et al 2002).…”

“…Com essa propriedade, a melatonina é capaz de eliminar os radicais livres gerados na mitocôndria, além de reduzir a fuga de elétrons a partir da cadeia respiratória, diminuindo a formação de EROs (Leon et al 2004). A melatonina, além de ser capaz de proteger as mitocôndrias dos danos oxidativos, reduzindo o consumo de oxigênio, é capaz de melhorar o potencial da membrana e a produção do ânion superóxido, mantendo, ao mesmo tempo, a produção de ATP (Lopez et al 2009). …”

Mitochondrial Disorders Therapy: The Utility of Melatonin~!2009-11-18~!2010-01-21~!2010-06-23~!

“…Moreover, melatonin increased the activity of C-I separated by blue native polyacrylamide gel electrophoresis (PAGE). The effects of melatonin are of likely physiological significance since the indoleamine increased the mitochondria respiratory chain activity coupled to OXPHOS, which was reflected in an elevated ATP synthesis, either in normal mitochondria or in mitochondria depleted of ATP by cyanide incubation [127,159].…”

“…The different sources of melatonin are related to the different actions of the indoleamine: the pineal melatonin is mainly a mediator of the circadian cycles and circannual reproductive rhythms [123,124]; the extrapineal melatonin participates in the immune system modulation, anti-inflammatory mechanisms and antioxidant actions [5,125]. Interestingly, melatonin is concentrated by subcellular compartments including nucleus and mitochondria, the latter showing 100-200 times more melatonin than cytosol [126,127]. Therefore, melatonin is available in the mitochondrion, the cell organelle in which free radicals are being maximally generated, and can counteract a potential damage [128,129].…”