title: Mitochondrial kinases in Parkinson's disease: converging insights from neurotoxin and genetic models.
abstract: Alterations in mitochondrial biology have long been implicated in neurotoxin, and more recently, genetic models of parkinsonian neurodegeneration. In particular, kinase regulation of mitochondrial dynamics and turnover are emerging as central mechanisms at the convergence of neurotoxin, environmental and genetic approaches to studying Parkinson's disease (PD). Kinases that localize to mitochondria during neuronal injury include mitogen activated protein kinases (MAPK) such as extracellular signal regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK), protein kinase B/Akt, and PTEN-induced kinase 1 (PINK1). Although site(s) of action within mitochondria and specific kinase targets are still unclear, these signaling pathways regulate mitochondrial respiration, transport, fission-fusion, calcium buffering, reactive oxygen species (ROS) production, mitochondrial autophagy and apoptotic cell death. In this review, we summarize accelerating experimental evidence gathered over the last decade that implicate a central role for kinase signaling at the mitochondrion in Parkinson's and related neurodegenerative disorders. Interactions involving alpha-synuclein, leucine rich repeat kinase 2 (LRRK2), DJ-1 and Parkin are discussed. Converging mechanisms from different model systems support the concept of common pathways in parkinsonian neurodegeneration that may be amenable to future therapeutic interventions.
authors: Dept. of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, United States of America.
authors: Ruben K
authors: RK
authors: Dagda
authors: Jianhui
authors: J
authors: Zhu
authors: Charleen T
authors: CT
authors: Chu
mesh_terms: D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000473:pathology*; D010770:Phosphotransferases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D024101:Mitochondrial Proteins; D010770:Phosphotransferases