RESEARCH ARTICLE


Mitochondrial Disorders Therapy: The Utility of Melatonin



Luis C. Lopez1, 2, Dario Acuna-Castroviejo1, 2, 3, Alberto del Pino1, 2, Miguel Tejada1, 2, Germaine Escames*, 1, 2
1 Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
2 Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain
2 Servico de Análisis Clínicos, Hospital Universitario San Cecilio, Granada, Spain


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© 2010 López et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain; Tel: +34958241000, Ext. 20197; Fax: +34958819132; E-mail: gescames@ugr.es


Abstract

Mitochondria play a central role in the cell physiology. It is now recognized that, besides their classic function of energy metabolism, mitochondria are enrolled in multiple cell functions including energy distribution through the cell, energy/heat modulation, reactive oxygen species (ROS) regulation, calcium homeostasis, and apoptosis control. Recently, evidence is accumulating for a direct participation of mitochondria in stem cell proliferation and/or differentiation. All these functions suggest that mutations in either nuclear or mitochondrial DNA may induce serious cell impairments, and there is now evidence of more than 200 mtDNA mutations responsible for human pathologies. Moreover, mitochondria are, simultaneously, the main producer and target of ROS and, thus, multiple mitochondrial diseases are related to ROSinduced mitochondrial injuries. Among these, neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), inflammatory diseases such as sepsis, and aging itself, are caused or accompanied by ROS-induced mitochondrial dysfunctions. With regard to its action spectrum as an antioxidant, melatonin may be regarded as a firstchoice agent for preventing and/or reducing the excess of ROS, thereby maintaining mitochondrial homeostasis. Multiple in vitro and in vivo experiments have shown the protective role of melatonin on mitochondrial physiology, yielding a significant improvement in those diseases in which energy supply to the cell had been compromised. New lines of evidence suggest the participation of mitochondria in stem cell proliferation and differentiation, and preliminary data support the role of melatonin in these processes. This review accounts for the multiple functions of mitochondria and the mechanisms involved in the numerous beneficial effects of melatonin to maintain mitochondrial homeostasis.

Keywords: Oxidative stress, aging, mitodhondrial dysfunction, neurodegenerative diseases, stem cell differentiation, melatonin therapy.