Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics.

Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine -acetyltransferase/serotonin -acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant.

On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species.

Melatonin is a phylogenetically ancient molecule. It is ubiquitously present in almost all organisms from primitive photosynthetic bacteria to humans. Its original primary function is presumable to be that of an antioxidant with other functions of this molecule having been acquired during evolution.

CSF generation by pineal gland results in a robust melatonin circadian rhythm in the third ventricle as an unique light/dark signal.

Pineal gland is an important organ for the regulation of the bio-clock in all vertebrate species. Its major secretory product is melatonin which is considered as the chemical expression of darkness due to its circadian peak exclusively at night. Pineal melatonin can be either released into the blood stream or directly enter into the CSF of the third ventricle via the pineal recess.

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism.

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured.

Melatonin: an ancient molecule that makes oxygen metabolically tolerable.

Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, anti-inflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.

Ebola virus disease: potential use of melatonin as a treatment.

The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus. The pathological changes associated with an Ebola infection include, most notably, endothelial disruption, disseminated intravascular coagulation and multiple organ hemorrhage. Melatonin has been shown to target these alterations.

Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: relation to their biological functions.

Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates.

Melatonin identified in meats and other food stuffs: potentially nutritional impact.

Melatonin has been identified in primitive photosynthetic bacteria, fungi, plants, and animals including humans. Vegetables, fruits, cereals, wine, and beers all contain melatonin. However, the melatonin content in meats has not been reported previously.

Melatonin in the biliary tract and liver: health implications.

Melatonin is a widely-produced and ubiquitously-distributed molecule with multiple critical functions in all organs and organisms. These functions are mediated by both receptor-mediated and receptor-independent actions of the indole. This survey reviews the reports documenting the presence and function of melatonin in the hepatobiliary system.

A walnut-enriched diet reduces the growth of LNCaP human prostate cancer xenografts in nude mice.

It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.

Peripheral reproductive organ health and melatonin: ready for prime time.

Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent. This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation.

The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives.

Melatonin is an uncommonly widely distributed molecule. It is found throughout the plant and animal kingdoms, i.e.

Mitochondria and chloroplasts as the original sites of melatonin synthesis: a hypothesis related to melatonin's primary function and evolution in eukaryotes.

Mitochondria and chloroplasts are major sources of free radical generation in living organisms. Because of this, these organelles require strong protection from free radicals and associated oxidative stress. Melatonin is a potent free radical scavenger and antioxidant.

Alterations in Lipid Levels of Mitochondrial Membranes Induced by Amyloid-β: A Protective Role of Melatonin.

Alzheimer pathogenesis involves mitochondrial dysfunction, which is closely related to amyloid-β (Aβ) generation, abnormal tau phosphorylation, oxidative stress, and apoptosis. Alterations in membranal components, including cholesterol and fatty acids, their characteristics, disposition, and distribution along the membranes, have been studied as evidence of cell membrane alterations in AD brain. The majority of these studies have been focused on the cytoplasmic membrane; meanwhile the mitochondrial membranes have been less explored.

Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: a protective role for melatonin.

Amyloid-beta (Aβ) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer's disease (AD) brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell.

Emergence of naturally occurring melatonin isomers and their proposed nomenclature.

Melatonin was considered to be the sole member of this natural family. The emergence of naturally occurring melatonin isomers (MIs) has opened an exciting new research area. Currently, several MIs have been identified in wine, and these molecules are believed to be synthesized by either yeasts or bacteria.

Alzheimer's disease: pathological mechanisms and the beneficial role of melatonin.

Alzheimer's disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition.

Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science.

The presence of melatonin in plants is universal. Evidence has confirmed that a major portion of the melatonin is synthesized by plants themselves even though a homologue of the classic arylalkylamine N-acetyltransferase (AANAT) has not been identified as yet in plants. Thus, the serotonin N-acetylating enzyme in plants may differ greatly from the animal AANAT with regard to sequence and structure.

Neurotoxins: free radical mechanisms and melatonin protection.

Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA.

Significance of high levels of endogenous melatonin in Mammalian cerebrospinal fluid and in the central nervous system.

Levels of melatonin in mammalian circulation are well documented; however, its levels in tissues and other body fluids are yet only poorly established. It is obvious that melatonin concentrations in cerebrospinal fluid (CSF) of mammals including humans are substantially higher than those in the peripheral circulation. Evidence indicates that melatonin produced in pineal gland is directly released into third ventricle via the pineal recess.

Cardiac hypertrophy and remodelling: pathophysiological consequences and protective effects of melatonin.

This survey summarizes the limited findings related to the ability of endogenously produced and exogenously administered melatonin to modify the response of the heart musculature to pathological situations that are normally accompanied by hypertrophy of the cardiomyocytes and alterations in cardiovascular physiology. Whereas melatonin did not reduce left ventricular hypertrophy in spontaneously hypertensive rats or in nitric oxide-deficient hypertension, it did have other beneficial effects, e.g.

The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness.

Melatonin is a molecule present in a multitude of taxa and may be ubiquitous in organisms. It has been found in bacteria, unicellular eukaryotes, macroalgae, fungi, plants and animals. A primary biological function of melatonin in primitive unicellular organisms is in antioxidant defence to protect against toxic free radical damage.

Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin.

The discovery of melatonin and its derivatives as antioxidants has stimulated a very large number of studies which have, virtually uniformly, documented the ability of these molecules to detoxify harmful reactants and reduce molecular damage. These observations have clear clinical implications given that numerous age-related diseases in humans have an important free radical component. Moreover, a major theory to explain the processes of aging invokes radicals and their derivatives as causative agents.

Melatonin and reproduction revisited.

This brief review summarizes new findings related to the reported beneficial effects of melatonin on reproductive physiology beyond its now well-known role in determining the sexual status in both long-day and short-day seasonally breeding mammals. Of particular note are those reproductive processes that have been shown to benefit from the ability of melatonin to function in the reduction of oxidative stress. In the few species that have been tested, brightly colored secondary sexual characteristics that serve as a sexual attractant reportedly are enhanced by melatonin administration.