Reduction of the mitochondria-localized protein p13 protects against experimental parkinsonism

抄録

Parkinson's disease (PD) is caused by the specific loss of nigrostriatal dopaminergic neurons. Mitochondrial toxins produce cellular and behavioral deficits resembling those in PD patients. Causative gene products for familial PD are involved in mitochondrial function. Thus, targeting proteins regulating mitochondrial integrity could provide convincing strategies for PD therapeutics. A novel 13-kDa protein (p13), we have recently identified, was suggested to control mitochondrial function. Here, we study the mitochondrial function of p13 and its roles in PD pathogenesis using mitochondrial toxin-induced PD models. We show that p13 overexpression induces mitochondrial dysfunction and apoptosis, whereas its knockdown attenuates both in dopaminergic SH-SY5Y cells via the regulation of complex I. Importantly, we generate p13-deficient mice using the CRISPR/Cas9 system and observe that heterozygous p13 knockout prevents toxin-induced motor deficits and the loss of nigral dopaminergic neurons. Accordingly, these results suggest that manipulating p13 expression may be a promising avenue for therapeutic intervention in PD.