Oxidative phosphorylation mediated pathogenesis of Parkinson's disease and its implication via Akt signaling.

Substantia Nigra Pars-compacta (SNpc), in the basal ganglion region, is a primary source of dopamine release. These dopaminergic neurons require more energy than other neurons, as they are highly arborized and redundant. Neurons meet most of their energy demand (∼90%) from mitochondria. Oxidative phosphorylation (OxPhos) is the primary pathway for energy production. Many genes involved in Parkinson's disease (PD) have been associated with OxPhos, especially complex I. Abrogation in complex I leads to reduced ATP formation in these neurons, succumbing to death by inducing apoptosis. This review discusses the interconnection between complex I-associated PD genes and specific mitochondrial metabolic factors (MMFs) of OxPhos. Interestingly, all the complex I-associated PD genes discussed here have been linked to the Akt signaling pathway; thus, neuron survival is promoted and smooth mitochondrial function is ensured. Any changes in these genes disrupt the Akt pathway, which hampers the opening of the permeability transition pore (PTP) via GSK3β dephosphorylation; promotes destabilization of OxPhos; and triggers the release of pro-apoptotic factors.