Parkinson’s Disease-Associated Mutations Affect Mitochondrial Function

Parkinson’s disease (PD) is an aging disorder of the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). The occurrence of PD is mostly sporadic, but it has also been linked to environmental factors and genetic mutations. Many studies have identified several susceptibility genes and loci related to PD such as α-Synuclein, parkin, DJ-1, PINK1, LRRK2, and ATP13A2. Mitochondria are essential organelles for cellular function due to their role in ATP production, calcium homeostasis, and apoptotic signaling. There is increasing evidence that mitochondrial dysfunctions play an essential role in the course of PD. Postmortem studies have shown mitochondrial deficiency, reduced complex I activity, and oxidative damage in idiopathic PD brains. Moreover, the study of animal models has generated valuable information regarding these pathogenic mechanisms underlying dopaminergic degeneration in PD, many of which point toward the involvement of mitochondrial dysfunction. The elucidation of the pathogenic mechanisms underlying the selective dopaminergic degeneration in PD is a priority at this point. In this chapter, we summarize how PD-causing mutations affect mitochondrial function, their roles in mitochondrial biogenesis, physiology, and dynamics, as well as in quality control, and consider how these mechanisms may be operative in sporadic PD.