Mitochondria: Oxidative stress, Dysfunction, and Cell death

Abstract

Mitochondrial research is presently one of the fastest growing disciplines in biomedicine. In mitochondria, reactive oxygen species (ROS) are generated as undesirable side products of the oxidative energy metabolism. It has been hypothesized that major factor in the dysfunction of mitochondria results from the defects in oxidative phosphorylation (OXPHOS) that results in the stimulation of the mitochondrial production of ROS and damage to mitochondrial DNA (mt DNA). Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target against oxidant-induced damage. Recent experimental and clinical studies have suggested the increased productions of oxygen radicals in human diseases with or with out preserving the antioxidant status. Inhibition of oxidative stress and mtDNA damage could be novel and effective treatment strategies for many diseases including heart failure. There are evidences of beneficial effect of certain antioxidants such as Coenzyme Q10, selenium, carvediol, L-acetyl-carnitine, α-lipoic acid, vitamin E to alleviate the oxidative stress in mitochondria associated with many diseases. Over expression of the genes for peroxiredoxin-3, a mitochondrial antioxidant, or mitochondrial transcription factor A, could ameliorate the decline in mtDNA copy number. Based on the recent exciting developments in mitochondrial research, increasing pharmacological efforts have been made leading to the emergence of ‘Mitochondrial Medicine’. The targeted and carrier-based delivery of drugs and DNA to mitochondria hardly constitutes a field of research on its own yet and is still in its infancy.