Human Molecular Genetics Advance Access originally published online on October 5, 2005
Human Molecular Genetics 2005 14(22):3477-3492; doi:10.1093/hmg/ddi377
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Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism
1Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Milan, 2IRCCS CSS, Mendel Institute, Rome, 3Department of Experimental Medicine and Pathology, La Sapienza University, Rome and 4Vita-Salute San Raffaele University, Milan, Italy
* To whom correspondence should be addressed at: Human Molecular Genetics Unit, San Raffaele Scientific University Institute, DIBIT, Via Olgettina 58, 20132 Milan, Italy. Tel: +39 0226433502/4721/4947; Fax: +39 0226434767; Email: casari.giorgio{at}hsr.it
Received August 18, 2005; Accepted September 29, 2005
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.
These authors contributed equally.
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