PTEN-induced kinase 1 (PINKJ) is a recently identified gene, mutations of which cause levodopa-responsive parkinsonism. An overexpression of wild-type PINK1 protects neurons from stress-induced mitochondrial dysfunction and apoptosis. We studied the effects of PIAIK1 suppression using small interfering RNA (siRNA), which call inhibit PINK1 mRNA expression up to 87%,, and decrease PINKI protein up to 80% in human dopaminergic cell line SH-SY5Y. Incubation with PINKI siRNA decreased SH-SY5Y cell viability and significantly increased MPP+ or rotenone-induced cytotoxicity. Our results indicate that reduction in PINK1 expression call trigger apoptotic process that can be exacerbated by the presence of MPP+ or rotenone. These findings support the hypothesis that PINK1 participates in the protection of dopaminergic neurons. (c) 2005 Elsevier Inc. All rights reserved.