title: Detailed analysis of mitochondrial respiratory chain defects caused by loss of PINK1.
abstract: Mutations in PTEN-induced putative kinase 1 (PINK1) cause recessive forms of Parkinson's disease (PD). PINK1 acts upstream of parkin, regulating mitochondrial elimination (mitophagy) in cultured cells treated with mitochondrial uncouplers that cause mitochondrial depolarization. PINK1 loss-of-function decreases mitochondrial membrane potential, resulting in mitochondrial dysfunction, although the exact function of PINK1 in mitochondria has not been fully elucidated. We have previously found that PINK1 deficiency causes a decrease in mitochondrial membrane potential, which is not due to a proton leak, but to respiratory chain defects. Here, we examine mitochondrial respiratory chain defects in PINK1-deficient cells, and find both complex I and complex III are defective. These results suggest that mitochondrial respiratory chain defects may be associated with PD pathogenesis caused by mutations in the PINK1 gene.
authors.affiliation: Department of Applied Chemistry, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan. Electronic address: amo@nda.ac.jp.
authors.forename: Taku
authors.initials: T
authors.lastname: Amo
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Saiki
authors.affiliation: Department of Applied Chemistry, National Defense Academy, 1-10-20 Hashirimizu, Yokosuka 239-8686, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sawayama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D045222:Electron Transport Chain Complex Proteins; D011494:Protein Kinases; D050994:Voltage-Dependent Anion Channels; D000099202:PTEN-Induced Putative Kinase
keywords: Mitochondria; PINK1; Parkinson's disease; Respiratory chain