title: The mitochondrial kinase PINK1, stress response and Parkinson's disease.
abstract: Mitochondrial dysfunction is well documented in presymptomatic brain tissue with Parkinson's disease (PD). Identification of the autosomal recessive variant PARK6 caused by loss-of-function mutations in the mitochondrial kinase PINK1 provides an opportunity to dissect pathogenesis. Although PARK6 shows clinical differences to PD, the induction of alpha-synuclein "Lewy" pathology by PINK1-deficiency proves that mitochondrial pathomechanisms are relevant for old-age PD. Mitochondrial dysfunction is induced by PINK1 deficiency even in peripheral tissues unaffected by disease, consistent with the ubiquitous expression of PINK1. It remains unclear whether this dysfunction is due to PINK1-mediated phosphorylation of proteins inside or outside mitochondria. Although PINK1 deficiency affects the mitochondrial fission/fusion balance, cell stress is required in mammals to alter mitochondrial dynamics and provoke apoptosis. Clearance of damaged mitochondria depends on pathways including PINK1 and Parkin and is critical for postmitotic neurons with high energy demand and cumulative stress, providing a mechanistic concept for the tissue specificity of disease.
authors: Klinik für Neurologie, Goethe Universität, Haus 89, Heinrich-Hoffmann-Str. 7, 60590, Frankfurt/M, Germany.
authors: Marina
authors: M
authors: Jendrach
authors: Suzana
authors: S
authors: Gispert
authors: Filomena
authors: F
authors: Ricciardi
authors: Michael
authors: M
authors: Klinkenberg
authors: Rudolf
authors: R
authors: Schemm
authors: Georg
authors: G
authors: Auburger
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D024101:Mitochondrial Proteins / Q000502:physiology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000172:deficiency* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D000099202:PTEN-Induced Putative Kinase
chemical_list: D024101:Mitochondrial Proteins; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein