TY - JOUR
T1 - Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism
AU - Silvestri, Laura
AU - Caputo, Viviana
AU - Bellacchio, Emanuele
AU - Atorino, Luigia
AU - Dallapiccola, Bruno
AU - Valente, Enza Maria
AU - Casari, Giorgio
PY - 2005/11/15
Y1 - 2005/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=27944444154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27944444154&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddi377
DO - 10.1093/hmg/ddi377
M3 - Article
C2 - 16207731
AN - SCOPUS:27944444154
VL - 14
SP - 3477
EP - 3492
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 22
ER -