title: The mitochondrial kinase PINK1: functions beyond mitophagy.
abstract: Mutations in the genes encoding the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin cause autosomal recessive Parkinson's disease (PD). Pioneering work in Drosophila melanogaster revealed that the loss of PINK1 or Parkin function causes similar phenotypes including dysfunctional mitochondria. Further research showed that PINK1 can act upstream of Parkin in a mitochondrial quality control pathway to induce removal of damaged mitochondria in a process called mitophagy. Albeit the PINK1/Parkin-induced mitophagy pathway is well established and has recently been elucidated in great detail, its pathophysiological relevance is being debated. Mounting evidence indicates that PINK1 has additional functions, for example, in regulating complex I activity and maintaining neuronal viability in response to stress. Here, we discuss mitophagy-dependent and -independent functions of PINK1 and their possible role in PD pathogenesis. Mutations in the PINK1 gene, encoding a mitochondrial kinase, are associated with autosomal recessive Parkinson's disease. In this review, we summarize and discuss the functional roles of PINK1 in maintaining mitochondrial integrity, eliminating damaged mitochondria, and promoting cell survival. This article is part of a special issue on Parkinson disease.
authors.affiliation: Department of Neurology, University Hospital, RWTH Aachen University, Aachen, Germany. avoigt@ukaachen.de.
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
authors.affiliation: Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Germany.
authors.forename: Lena A
authors.initials: LA
authors.lastname: Berlemann
authors.affiliation: Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Germany. konstanze.winklhofer@rub.de.
authors.forename: Konstanze F
authors.initials: KF
authors.lastname: Winklhofer
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase
keywords: PINK1; Parkin; Parkinson's disease; mitochondria; mitophagy