title: Mercury and protein thiols: Stimulation of mitochondrial F1FO-ATPase and inhibition of respiration.
abstract: In spite of the known widespread toxicity of mercury, its impact on mitochondrial bioenergetics is a still poorly explored topic. Even if many studies have dealt with mercury poisoning of mitochondrial respiration, as far as we are aware Hg2+effects on individual complexes are not so clear. In the present study changes in swine heart mitochondrial respiration and F1FO-ATPase (F-ATPase) activity promoted by micromolar Hg2+concentrations were investigated. Hg2+was found to inhibit the respiration of NADH-energized mitochondria, whereas it was ineffective when the substrate was succinate. Interestingly, the same micromolar Hg2+doses which inhibited the NADH-O2activity stimulated the F-ATPase, most likely by interacting with adjacent thiol residues. Accordingly, Hg2+dose-dependently decreased protein thiols and all the elicited effects on mitochondrial complexes were reversed by the thiol reducing agent DTE. These findings clearly indicate that Hg2+interacts with Cys residues of these complexes and differently modulate their functionality by modifying the redox state of thiol groups. The results, which cast light on some implications of metal-thiol interactions up to now not fully explored, may contribute to clarify the molecular mechanisms of mercury toxicity to mitochondria.
authors: Department of Veterinary Medical Sciences, University of Bologna, Italy.
authors: Salvatore
authors: S
authors: Nesci
authors: Department of Veterinary Medical Sciences, University of Bologna, Italy.
authors: Fabiana
authors: F
authors: Trombetti
authors: Department of Veterinary Medical Sciences, University of Bologna, Italy.
authors: Maurizio
authors: M
authors: Pirini
authors: Department of Veterinary Medical Sciences, University of Bologna, Italy.
authors: Vittoria
authors: V
authors: Ventrella
authors: Department of Veterinary Medical Sciences, University of Bologna, Italy. Electronic address: alessandra.pagliarani@unibo.it.
authors: Alessandra
authors: A
authors: Pagliarani
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001152:Arsenicals; D019069:Cell Respiration / Q000187:drug effects; D004226:Dithioerythritol / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008628:Mercury / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D034421:Sus scrofa
chemical_list: D001152:Arsenicals; D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; C029341:oxophenylarsine; D004226:Dithioerythritol; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D008628:Mercury; D008274:Magnesium
keywords: F(1)F(O)-ATPase; Mercury; Mitochondria; Oxidative phosphorylation; Thiol groups