Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease

Abstract

: Melatonin is a natural occurring compound with well‐known antioxidant properties. Melatonin is ubiquitously distributed and because of its small size and amphiphilic nature, it is able to reach easily all cellular and subcellular compartments. The highest intracellular melatonin concentrations are found in mitochondria, raising the possibility of functional significance for this targeting with involvement in situ in mitochondrial activities. Mitochondria, the powerhouse of the cell, are considered to be the most important cellular organelles to contribute to degenerative processes mainly through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage to mitochondrial proteins, lipids and DNA. Therefore, protecting mitochondria from oxidative damage could be an effective therapeutic strategy against cellular degenerative processes. Many of the beneficial effects of melatonin administration may depend on its effect on mitochondrial physiology. Cardiolipin, a phospholipid located at the level of inner mitochondrial membrane is known to be intimately involved in several mitochondrial bioenergetic processes as well as in mitochondrial‐dependent steps of apoptosis. Alterations to cardiolipin structure, content and acyl chain composition have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological situations and aging. Recently, melatonin was reported to protect the mitochondria from oxidative damage by preventing cardiolipin oxidation and this may explain, at least in part, the beneficial effect of this molecule in mitochondrial physiopathology. In this review, we discuss the role of melatonin in preventing mitochondrial dysfunction and disease.

Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation

“…Melatonin has pleiotropic bioactivities including as a highly effective antioxidant and free radical scavenger (Beyer et al 1998, Gitto et al 2009, Chahbouni et al 2010, Paradies et al 2010. Melatonin has protective effect against heart and brain ischemia/reperfusion injuries depending on its antioxidant and free radical scavenging properties (Paradies et al 2010).…”

“…Melatonin has protective effect against heart and brain ischemia/reperfusion injuries depending on its antioxidant and free radical scavenging properties (Paradies et al 2010). Melatonin has a regulatory role in MMP-mediated physiological processes and major human diseases.…”

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Several reports have shown that melatonin improves mitochondrial function, reduces mitochondrial oxidative status, and increases the activity of the respiratory chain [146,148]. Melatonin, but not other antioxidants (e.g., vitamins C and E, N-acetylcysteine) is highly efficient in maintaining mitochondrial glutathione homeostasis in extremely oxidative conditions, closing the mitochondrial permeability transition pore [149] and promoting mitochondrial survival [150,151].…”

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

“…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] .…”