Mitochondria: Key Organelle in Parkinson’s Disease

Parkinsonu0027s disease (PD) is the second most common neurodegenerative disorder, characterized pathologically by loss of dopaminergic neurons in the substantia nigra pars compacta. The etiology of PD is still unknown, involving genetic and environmental factors; however mitochondrial dysfunction plays a central role in PD pathogenesis. In this regard, several PD-related proteins (PINK1, Parkin, DJ-1, LRRK2, and α-synuclein) are linked to mitochondrial function. Mitochondria are highly dynamic organelles involved in essential cellular functions, including energy production, calcium homeostasis, metabolism of amino acids and lipids, mtDNA replication, and programmed cell death. Moreover, mitochondrial homeostasis is tightly regulated by several pathways, including mitochondrial biogenesis, remodeling (fusion/fission), and clearance of damaged mitochondria by autophagy (mitophagy), among others. Mitochondrial dysfunction and the engagement of calcium channels during autonomous pacemaking have been implicated in the increased susceptibility of dopaminergic neurons to cell death in the substantia nigra.