Mitochondrial Import And Enzymatic Activity Of PINK1 Mutants Associated To Recessive Parkinsonism

Authors:
Laura Silvestri (1), Viviana Caputo (2,3), Emanuele Bellacchio (2), Luigia Atorino (1), Bruno Dallapiccola (2,3), Enza Maria Valente (2) and Giorgio Casari (1,4)

[Note: The first two authors contributed equally]

Affiliations:
(1) Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Milan,
(2) IRCCS CSS, Mendel Institute, Rome,
(3) Department of Experimental Medicine and Pathology, La Sapienza University, Rome
(4) Vita-Salute San Raffaele University, Milan, Italy

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.

Author Contact:

Giorgio Casari
Human Molecular Genetics Unit, San Raffaele Scientific University Institute, DIBIT, Via Olgettina 58, 20132 Milan, Italy.
Email: casari.giorgio@hsr.it

Free Full Text available at: PINK1 Paper.

(C) Human Molecular Genetics.

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