Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs

Oxidative stress, one of the crucial factors of genomic instability, is involved in many illnesses - from DNA damage and repair (DDR) related diseases to neurological abnormalities and cancer. Patients with defective DDR pathways display high level of cancer predisposition and at the same time - reveal hydrocephalia, dementias and even diabetes mellitus - all representing common hallmarks of mitochondria-related disorders. Since mitochondria are responsible both for the cell energetic metabolism and for reactive oxygen/nitrogen species (RO/NS) formation, mitochondrial dysfunction (MDF) play a pivotal role in the above disorders. Not surprisingly, RO/NS are considered to be a primary target for a large spectrum of compounds aiming to eliminate these adverse species or, in contrary, enhance their presence in order to amplify cellular death pathways. Yet, only few chemicals have received medical appreciation mainly because of their questionable therapeutic values in healthy states. As a result, recent efforts have been focused on finding the drugs that improve mitochondrial functions or chemoprevent MDF rather than being applied as RO/NS scavengers. This review addresses the most recent progress in the development and application of such chemicals and outlines some future perspectives. Keywords: Apoptosis, chemoprevention, mitochondria, mitophagy, oxidative stress, RNS, ROS.