title: A mitocentric view of Parkinson's disease.
abstract: Parkinson's disease (PD) is a common neurodegenerative disease, yet the underlying causative molecular mechanisms are ill defined. Numerous observations based on drug studies and mutations in genes that cause PD point to a complex set of rather subtle mitochondrial defects that may be causative. Indeed, intensive investigation of these genes in model organisms has revealed roles in the electron transport chain, mitochondrial protein homeostasis, mitophagy, and the fusion and fission of mitochondria. Here, we attempt to synthesize results from experimental studies in diverse systems to define the precise function of these PD genes, as well as their interplay with other genes that affect mitochondrial function. We propose that subtle mitochondrial defects in combination with other insults trigger the onset and progression of disease, in both familial and idiopathic PD.
authors.affiliation: Program in Developmental Biology.
authors.forename: Nele A
authors.initials: NA
authors.lastname: Haelterman
authors.forename: Wan Hee
authors.initials: WH
authors.lastname: Yoon
authors.forename: Hector
authors.initials: H
authors.lastname: Sandoval
authors.forename: Manish
authors.initials: M
authors.lastname: Jaiswal
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Shulman
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*
chemical_list: D009419:Nerve Tissue Proteins
keywords: PD genes; electron transport chain; mitochondria; mitochondrial dynamics; mitochondrial unfolded protein response; reactive oxygen species