title: The Parkinson Disease Mitochondrial Hypothesis: Where Are We at?
abstract: Parkinson's disease is a common, adult-onset neurodegenerative disorder whose pathogenesis is still under intense investigation. Substantial evidence from postmortem human brain tissue, genetic- and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of the disease. This review discusses our current understanding of Parkinson's disease-related mitochondrial dysfunction, including bioenergetic defects, mitochondrial DNA alterations, altered mitochondrial dynamics, activation of mitochondrial-dependent programmed cell death, and perturbations in mitochondrial tethering to the endoplasmic reticulum. Whether a primary or secondary event, mitochondrial dysfunction holds promise as a potential therapeutic target to halt the progression of neurodegeneration in Parkinson's disease.
authors.affiliation: Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franco-Iborra
authors.affiliation: Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Vila
authors.affiliation: Vall d'Hebron Research Institute-CIBERNED, Barcelona, Spain celine.perier@vhir.org.
authors.forename: Celine
authors.initials: C
authors.lastname: Perier
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism*; D063306:Mitophagy; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial
keywords: apoptosis; complex I; fusion/fission; mitochondria-associated endoplasmic reticulum membranes; mtDNA