Mitochondrial Dysfunction

Mitochondria are primarily important for the generation of cellular energy through oxidative phosphorylation. Byproducts of this process are reactive oxygen species that can cause cell damage if not appropriately regulated. Mitochondria also play roles in other cellular functions including buffering of critical intracellular signaling pathways and molecules (such as calcium) and regulation of cell death pathways.

Image from NINDS, NIHEvidence that mitochondrial dysfunction plays a role in PD comes primarily through the recognition that levels and activity of Complex I, the first enzyme complex in the oxidative phosphorylation pathway, are reduced in post mortem substantia nigra brain tissue from patients with PD. Loss of Complex I can lead to reduced energy production and increased generation of damaging free radicals. Some evidence suggests that mutations and polymorphisms in mitochondrial DNA, which codes for a number of components of the electron transport chain, are also found in people with PD and are potentially associated with PD risk. However, these results are controversial (Schapira, 2008).

Some of the genes associated with PD-related mitochondrial dysfunction are PINK1, LRRK2, DJ-1, and POLG-1.