Mitochondrial metabolism of reactive oxygen species

Abstract

Oxidative stress is considered a major contributor to etiology of both "normal" senescence and severe pathologies with serious public health implications. Mitochondria generate reactive oxygen species (ROS) that are thought to augment intracellular oxidative stress. Mitochondria possess at least nine known sites that are capable of generating superoxide anion, a progenitor ROS. Mitochondria also possess numerous ROS defense systems that are much less studied. Studies of the last three decades shed light on many important mechanistic details of mitochondrial ROS production, but the bigger picture remains obscure. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal. An integrative, systemic approach is applied to analysis of mitochondrial ROS metabolism, which is now dissected into mitochondrial ROS production, mitochondrial ROS removal, and mitochondrial ROS emission. It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.

Synoviocytes, not chondrocytes, release free radicals after cycles of anoxia/re-oxygenation

“…The EPR signals that we reported here were similar to those obtained with isolated mitochondria, and suggested a mitochondrial origin: the observed EPR spectra of POBN/ethoxy adducts can be attributed to the reaction of superoxide anion by-product with ethanol in the presence of the spin trap agent [7]. Indeed, mitochondria are reported to produce superoxide anion and other ROS in normal as well as in pathological conditions of A/R [7][8][9]. The superoxide anion that is produced on the matrix side of the mitochondrial membrane can cause cell damage (e.g., lipid peroxidation) by reacting with metal iron complexes within the enzymatic domain.…”

“…Superoxide anion can also react with nitric oxide (NO Å ), of which the production is recognised in mitochondria and increases with increased Ca 2+ concentrations, such as during anoxia [9,11]. From this reaction, peroxynitrite can be formed, from which new radical species are generated, such as hydroxyl radicals, favouring the peroxidation of membrane phospholipids and generating lipidic radical species.…”

Mitochondria and aging: A role for the mitochondrial transition pore?

“…The electron leakage in the electron transport chain during respiration is generally considered as the main source of mitochondrial ROS but other mitochondrial enzymatic systems, such as monoamine oxidase and cytochrome b5 reductase in the outer membranes, cytochromes P450 enzymes in the inner membranes, or several matrix enzymes such as aconitase, can also produce ROS (Andreyev, Kushnareva, Murphy, & Starkov, 2015; Andreyev, Kushnareva, & Starkov, 2005). Although mitochondria are not always considered as the main producer of ROS in the cell (NADPH or xantine oxidases being able to produce high levels of ROS), the respiratory chain produces ROS continuously.…”

Prohibitin involvement in the generation of mitochondrial superoxide at complex I in human sperm

“…For example in somatic cells, the major source of ROS generation is electron leakage from mitochondrial electron transport chain (ETC) during cellular respiration 1. However, once the fine balance controlled by antioxidant factors within the inter‐membrane space and mitochondrial matrix 2 is lost, mitochondrial ROS production may generate oxidative stress that has been implicated in numerous pathological conditions, including Alzheimer's 3 and Parkinson's disease 4. Current evidence supports the generation of ROS by sperm mitochondria in rabbits 5, 6, rats 7 and human 8, but the factors responsible for excessive mitochondrial free radical generation remains unidentified.…”