Mitochondrial complex I and nitric oxide synthase as main markers of ´complex I syndrome` in Parkinson´s disease

Abstract

Parkinson?s disease (PD) is the second most prevalent neurodegenerative disorder, and it is characterized by the progressive degeneration of the dopaminergic neurons located in the substantia nigra pars compacta, striatum body and brain cortex. Multiple -genetic and environmental- factors contribute to the appearance of PD; however, mitochondrial dysfunction with the decreased capacity to produce ATP and oxidative damage are pathognomonic characteristics always present in the affected brain areas. Mitochondrial dysfunction includes the concomitant reduction in the active respiration sustained by malate-glutamate and in the complex I activity, accompanied by changes in mtNOS biochemical (i.e. mitochondrial NO production) and functional activities, enhancement in mitochondrial O2- and H2O2 production rates, and increase in the contents of phospholipid peroxidation products and protein oxidation. Mitochondrial dynamics is also impaired in neurodegenerative diseases, not only because of the altered synthesis of new mitochondria (mitochondrial biogenesis), but also the distorted degradation of damaged mitochondria (mitophagy), making the situation even more adverse due to the accumulation of dysfunctional mitochondria. The mitochondrial dysfunction observed in PD agrees with the complex I syndrome concept, showing the high sensitivity of mitochondrial complex I to inactivation by oxidative reactions.