Oxidative Stress and Mitochondrial Dysfunction

Dear Colleagues,

Mitochondria are the major source of reactive oxygen species (ROS) within the cell. Electron leakage from complexes I and III of the mitochondrial respiratory chain (MRC) causes partial reduction of molecular oxygen to superoxide, which is then dismutated to hydrogen peroxidase by superoxide dismutase. Both superoxide and hydrogen peroxide are considered to be mitochondrial ROS. Under physiological conditions, ROS act as potential secondary messengers that can specifically modulate distinct cellular pathways, including the innate immune signaling cascade. However, once the level of ROS production exceeds the scavenging capacity of the cellular antioxidant defense system, a condition known as oxidative stress (OS) arises. This is an inherited genetic disorder and can induce secondary mitochondrial dysfunction, as opposed to primary mitochondrial dysfunction. OS can also induce DNA mutations, impair MRC activity, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial internal defense mechanisms. This leads to impairment of mitochondrial function and contributes to disease pathophysiology. OS and mitochondrial dysfunction have been implicated in the progression of many diseases including neurodegenerative disorders, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, metabolic diseases such as MRC disorders and lysosomal storage disorders, diabetes, cardiovascular diseases and cancer. The use of appropriate antioxidant adjunct therapies may be particularly important for the treatment of diseases associated with mitochondrial dysfunction and OS, although treatment protocols have yet to be fully established and standardized. Since mitochondria are a major contributor to cellular OS in the disease state, antioxidant strategies that target this organelle may offer promising therapeutic potential.  However, excessive administration of antioxidants can inhibit ROS-dependent signaling pathways and prevent the induction of endogenous antioxidant defense systems. In order to detect evidence of OS in patients and to ensure appropriate levels of antioxidant therapy, non-invasive assessment of plasma or white blood cell antioxidant status, or of the stable end-products of lipid, DNA or protein oxidation will be required. However, these techniques may only be available at specialist centers or on an ad hoc basis. Therefore, it is important to develop a consensus and a unified approach for monitoring OS in patients and for developing appropriate therapeutic strategies that target OS in disease.

The aim of this Special Issue is to highlight appropriate antioxidant therapeutic strategies that target the mitochondria and attenuate OS in disease. This Special Issue will also focus on suitable techniques with low invasiveness for assessing OS in patients.

Dr. Iain P. Hargreaves and Dr. Robert Heaton

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