title: Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance.
abstract: Copper is an essential transition metal ion for the function of key metabolic enzymes, but its uncontrolled redox reactivity is source of reactive oxygen species. Therefore a network of transporters strictly controls the trafficking of copper in living systems. Deficit, excess, or aberrant coordination of copper are conditions that may be detrimental, especially for neuronal cells, which are particularly sensitive to oxidative stress. Indeed, the genetic disturbances of copper homeostasis, Menkes' and Wilson's diseases, are associated with neurodegeneration. Furthermore, copper interacts with the proteins that are the hallmarks of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and familial amyotrophic lateral sclerosis. In all cases, copper-mediated oxidative stress is linked to mitochondrial dysfunction, which is a common feature of neurodegeneration. In particular we recently demonstrated that in copper deficiency, mitochondrial function is impaired due to decreased activity of cytochrome c oxidase, leading to production of reactive oxygen species, which in turn triggers mitochondria-mediated apoptotic neurodegeneration.
authors.affiliation: Department of Biology, "Tor Vergata" University of Rome, Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Rossi
authors.forename: Marco F
authors.initials: MF
authors.lastname: Lombardo
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ciriolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rotilio
mesh_terms: D000818:Animals; D017209:Apoptosis; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D017240:Mitochondrial Myopathies / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D003300:Copper