title: Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1 mutations confer different autophosphorylation activity, which is regulated by the C-terminal portion of the protein. We also demonstrate the mitochondrial localization of both wild-type and mutant PINK1 proteins unequivocally and prove that a short N-terminal part of PINK1 is sufficient for its mitochondrial targeting.
authors.affiliation: Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Silvestri
authors.forename: Viviana
authors.initials: V
authors.lastname: Caputo
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.forename: Luigia
authors.initials: L
authors.lastname: Atorino
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casari
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D018389:Codon, Nonsense; D005808:Genes, Recessive; D006367:HeLa Cells; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000201:enzymology* / Q000235:genetics*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012995:Solubility; D000099202:PTEN-Induced Putative Kinase
chemical_list: D018389:Codon, Nonsense; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase