title: OXPHOS toxicogenomics and Parkinson's disease.
abstract: Activities and quantities of several oxidative phosphorylation (OXPHOS) system complexes are decreased in many Parkinson's disease (PD) patients. Mutations in PD-associated nuclear genes affect OXPHOS function. Moreover, the inactivation of other nuclear genes related to mitochondrial DNA (mtDNA) replication and expression also leads to Parkinsonism. MtDNA only encodes OXPHOS subunits and the RNAs required for their expression. Mutations in mtDNA genes have also been associated with PD. Furthermore, many xenobiotics that inhibit different OXPHOS complexes provoke Parkinsonism. The binding sites for these venoms are usually mtDNA-encoded subunits. However, and despite the existence of mutations or toxicants that can cause Parkinsonism, PD only rarely results from isolated genetic or environmental factors. Combinations of nuclear and mitochondrial genetic and environmental factors have additive effects and increase the risk of PD. It is also possible that population polymorphisms in mtDNA genes, affecting interactions with different xenobiotics, may behave as susceptibility factors for developing PD only in the presence of that particular xenobiotic. Therefore, a deeper analysis of the OXPHOS function in PD is required if we want to unravel the complexities of this disorder.
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: López-Gallardo
authors.forename: Ruth
authors.initials: R
authors.lastname: Iceta
authors.forename: Eldris
authors.initials: E
authors.lastname: Iglesias
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
mesh_terms: D004272:DNA, Mitochondrial / Q000502:physiology; D059647:Gene-Environment Interaction; D006801:Humans; D009154:Mutation; D010085:Oxidative Phosphorylation; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D043922:Toxicogenetics; D015262:Xenobiotics / Q000009:adverse effects
chemical_list: D004272:DNA, Mitochondrial; D015262:Xenobiotics