Mitochondria and reactive oxygen species. Which role in physiology and pathology?

Oxidative stress is among the major causes of toxicity due to interaction of Reactive Oxygen Species (ROS) with cellular macromolecules and structures and interference with signal transduction pathways. The mitochondrial respiratory chain, specially from Complexes I and III, is considered the main origin of ROS particularly under conditions of high membrane potential, but several other sources may be important for ROS generation, such as mitochondrial p66(Shc), monoamine oxidase, α-ketoglutarate dehydogenase, besides redox cycling of redox-active molecules. ROS are able to oxidatively modify lipids, proteins, carbohydrates and nucleic acids in mitochondria and to activate/inactivate signalling pathways by oxidative modification of redox-active factors. Cells are endowed with several defence mechanisms including repair or removal of damaged molecules, and antioxidant systems, either enzymatic or non-enzymatic. Oxidative stress is at the basis of ageing and many pathological disorders, such as ischemic diseases, neurodegenerative diseases, diabetes, and cancer, although the underlying mechanisms are not always completely understood.