title: Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition.
abstract: Melatonin, a metabolic product of the amino acid tryptophan, induces a dose-dependent energy drop correlated with a decrease in the oxidative phosphorylation process in isolated rat liver mitochondria. This effect involves a gradual decrease in the respiratory control index and significant alterations in the state 4/state 3 transition of membrane potential (ΔΨ). Melatonin, alone, does not affect the insulating properties of the inner membrane but, in the presence of supraphysiological Ca2+, induces a ΔΨ drop and colloid-osmotic mitochondrial swelling. These events are sensitive to cyclosporin A and the inhibitors of Ca2+ transport, indicative of the induction or amplification of the mitochondrial permeability transition. This phenomenon is triggered by oxidative stress induced by melatonin and Ca2+, with the generation of hydrogen peroxide and the consequent oxidation of sulfydryl groups, glutathione and pyridine nucleotides. In addition, melatonin, again in the presence of Ca2+, can also induce substantial release of cytochrome C and AIF (apoptosis-inducing factor), thus revealing its potential as a pro-apoptotic agent.
authors.affiliation: Department of Biological Chemistry, University of Padua, Viale G. Colombo 3, 35121, Padua, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Martinis
authors.forename: L
authors.initials: L
authors.lastname: Zago
authors.forename: M
authors.initials: M
authors.lastname: Maritati
authors.forename: V
authors.initials: V
authors.lastname: Battaglia
authors.forename: S
authors.initials: S
authors.lastname: Grancara
authors.forename: V
authors.initials: V
authors.lastname: Rizzoli
authors.forename: E
authors.initials: E
authors.lastname: Agostinelli
authors.forename: M
authors.initials: M
authors.lastname: Bragadin
authors.forename: A
authors.initials: A
authors.lastname: Toninello
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects*; D051381:Rats
chemical_list: C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D016572:Cyclosporine; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D008550:Melatonin; D002118:Calcium