Melatonin-mitochondria Interplay in Health and Disease.

[Guest guest]

I am trying to puzzle together some of the mystery that is my son's dependence on melatonin - which has always worried me - he simply is unable to function without it.   And I don't mean just sleep, I mean that he is dependent on it for a vastly improved quality of life. This is deeply puzzling to me as I have yet to encounter any other ASD child with a similar response.  He presents with some symptoms that a paed neurologist speculated could be metabolic or mitochondrial in orgin (a neuromuscular issue) and I wonder if there is some correlation between the oxidative stress / nitrosative stress aspects of melatonin and his possible meta/mito issues.  

I would really like to read these full articles - is there anyone who might have access who would kindly be able to access it for me?  Or does anyone know how I might pay to access them? (these are pubmed searches)

Melatonin-mitochondria Interplay in Health and Disease.

Castroviejo DA, López LC, Escames G, López A, García JA, Reiter RJ.

Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain. dacuna@....

Abstract

Although two main hypotheses of mitochondrial origin have been proposed, i.e., the autogenous and the endosymbiotic, only the second is being seriously considered currently. The 'hydrogen hypothesis' invokes metabolic symbiosis as the driving force for a symbiotic association between an anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the symbiont) that was able to respire, but which generated molecular hydrogen as an end product of anaerobic metabolism. The resulting proto-eukaryotic cell would have acquired the essentials of eukaryotic energy metabolism, evolving not only aerobic respiration, but also the physiological cost of the oxygen consumption, i.e., generation of reactive oxygen species (ROS) and the associated oxidative damage. This is not the only price to pay for respiring oxygen: mitochondria possess nitric oxide (NO·) for regulatory purposes but, in some instances it may react with superoxide anion radical to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite anion, and the subsequent nitrosative damage. New mitochondria contain their own genome with a modified genetic code that is highly conserved among mammals. The transcription of certain mitochondrial genes may depend on the redox potential of the mitochondrial membrane. Mitochondria are related to the life and death of cells. They are involved in energy production and conservation, having an uncoupling mechanism to produce heat instead of ATP, but they are also involved in programmed cell death. Increasing evidence suggest the participation of mitochondria in neurodegenerative and neuromuscular diseases involving alterations in both nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful antioxidant and anti-inflammatory and increasing experimental and clinical evidence shows its beneficial effects against oxidative/nitrosative stress status, including that involving mitochondrial dysfunction. This review summarizes the data and mechanisms of action of melatonin in relation to mitochondrial pathologies.

Melatonin role in the mitochondrial function.

Acuna-Castroviejo D, Escames G,  MI,  LC.

S

Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...

Abstract

Melatonin is an ancient molecule present in unicellular organisms at the very early moment of life. Initially identified as a secretory product of the pineal gland in mammals and in other species, it was considered a hormone related to reproduction. The evidence that melatonin is produced in many organs and tissues of the body, reaching concentrations higher than in the blood, support the multiplicity of the melatonin actions. The best-known actions of melatonin, currently supported by experimental and clinical data, include antioxidant and anti-inflammatory abilities, some of them involving genomic regulation of a series of enzymes. Besides, melatonin displays anticonvulsant and antiexcitotoxic properties. Most of the beneficial consequences resulting from melatonin administration may depend on its effects on mitochondrial physiology. The physiological effects of melatonin on normal mitochondria, its role to prevent mitochondrial impairment, energy failure, and apoptosis in oxidatively-damaged mitochondria, and the beneficial effects of the administration of melatonin in experimental and clinical diseases involving mitochondrial dysfunction and cell death, are revised.