p13 protects against Parkinson's disease

Abstract

Mitochondrial dysfunction is thought to contribute to Parkinson's disease progression, and factors that can overcome mitochondrial defects could potentially be used to combat the disease and prevent neuronal death. In this issue, Inoue et al 1 report that reduction of p13, a mitochondrial protein that inhibits complex I assembly, rescues the cellular and behavioral defects of Parkinson's disease models. This work suggests that stabilizing the mitochondrial electron transport chain may be beneficial in the context of Parkinson's disease.

Figure 1. p13 downregulation promotes the assembly of mitochondrial complex I and prevents mitochondrial dysfunction and cell death in Parkinson's disease models

Parkinson's disease (PD) toxins, such as rotenone or MPTP, affect mitochondrial function: assembly of complex I (shown in orange) is decreased, mitochondrial membrane potential (Ψm) is reduced, and reactive oxygen species accumulate. This ultimately culminates in the degeneration of dopaminergic neurons in the substantia nigra. Reduction of p13 levels promotes the assembly of complex I, rescues the mitochondrial defects of PD models, and prevents neuronal death.