New perspectives on the role of mitochondria in Parkinson's disease

Mitochondrial dysfunction is pivotal in the occurrence and development of Parkinson's disease (PD). Interventions to increase mitochondrial biogenesis and maintain the balance in mitochondrial turnover have the potential to protect against neurological damage. In addition to their crucial role in the tricarboxylic acid cycle, mitochondria impact diverse activities, including cellular metabolism, cellular quality control, and the production of reactive oxygen species. Thus, it has become imperative to better understand the regulation and function of mitochondria in PD. With this review, we aim to stimulate research that explores mitochondria-oriented neuroprotection strategies to maintain the balance in mitochondrial turnover. First, we summarize research on newly discovered genes that regulate PD mitochondrial autophagy through PTEN-induced kinase 1 (PINK1), namely AMBRA1, SYNJ2BP, and SIAH3. Second, we review PD-related mitochondrial proteins, including STRT3 and SIRT6, and the mitochondrial unfolded protein response, covering their mechanisms of involvement in PD. Third, we emphasize the roles of the mitochondrial complex, pyroptosis, and copper-induced cell death in mitochondrial damage in PD. Finally, we present a brief overview of new therapeutic strategies to correct mitochondrial defects that may be applicable for targeting mitochondria in PD patients.