The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis

Figure 5

The different causes of mitochondrial dysfunction in the pathology of familial Parkinson’s diseases (PD). Some familial cases of PD include mutations in α-synuclein, PINK1-deficiency, and mutations in DJ1 (PARK7), leucine-rich repeat kinase 2 (LRRK2), and high-temperature requirement protein A2 (HTRA2). Mutations in α-synuclein result in the protein becoming localized in the mitochondria, causing mitochondrial dysfunction via oxidative stress, impaired Ca²⁺ signaling, complex I dysfunction, and mitochondrial fragmentation. PINK1 deficiency and mutations in LRRK2 also lead to impaired respiratory chain activity. Furthermore, LRRK2 mutations can reduce mitochondrial mobility and cause mtDNA damage. Mutations in DJ1 affect its role to regulate NFE2L2 degradation, resulting in the potential exacerbation of oxidative stress. Furthermore, HTRA2 mutations lead to the dysregulation and impairment of mitochondria-induced apoptosis.