Abstract
Oxidative stress arises when cellular antioxidant defences become overwhelmed by a surplus generation of reactive oxygen species (ROS). Once this occurs, many cellular biomolecules such as DNA, lipids, and proteins become susceptible to free radical-induced oxidative damage, and this may consequently lead to cellular and ultimately tissue and organ dysfunction. Mitochondria, as well as being a source of ROS, are vulnerable to oxidative stress-induced damage with a number of key biomolecules being the target of oxidative damage by free radicals, including membrane phospholipids, respiratory chain complexes, proteins, and mitochondrial DNA (mt DNA). As a result, a deficit in cellular energy status may occur along with increased electron leakage and partial reduction of oxygen. This in turn may lead to a further increase in ROS production. Oxidative damage to certain mitochondrial biomolecules has been associated with, and implicated in the pathophysiology of a number of diseases. It is the purpose of this review to discuss the impact of such oxidative stress and subsequent damage by reviewing our current knowledge of the pathophysiology of several inherited mitochondrial disorders together with our understanding of perturbations observed in the more commonly acquired neurodegenerative disorders such as Parkinson’s disease (PD). Furthermore, the potential use and feasibility of antioxidant therapies as an adjunct to lower the accumulation of damaging oxidative species and hence slow disease progression will also be discussed.
Highlights
Up to 90% of cellular metabolic energy is generated by mitochondria via the oxidative phosphorylation pathway [1]
The tricarboxylic acid (TCA) cycle generates a small amount of energy via substrate level phosphorylation, the vast proportion of metabolic energy is harnessed via the generation of reducing power and subsequent donation of high energy electron pairs through the electron carriers NADH and FADH2, which feed directly into mitochondrial respiratory chain (MRC)
The MRC is composed of four multi-subunit proteins; complex I (NADH: ubiquinone reductase; EC 1.6.5.3), complex II, complex III, and complex IV [2], each of which contain a variety of cofactors such as hemes, J
Summary
Up to 90% of cellular metabolic energy is generated by mitochondria via the oxidative phosphorylation pathway [1]. 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