Mitochondrial Production of ROS: Deviations from the “Standard Model”

Abstract

Since the discovery of mitochondrial ROS production by P.K. Jensen in 1966, numerous mechanistic details of this process have been revealed. The mainstream interpretation of the obtained data has shaped a “standard model” of mitochondrial ROS production, which, although lacking a formal description, is currently widely accepted. The “standard model” postulates that the major primary ROS generated in mitochondria is superoxide. This superoxide is predominantly generated by Complexes I and III of the respiratory chain, and possibly, a few other enzymes e.g., dihydrolipoamide dehydrogenase. Most of the data to support this concept have been obtained by inhibitor analysis with specific inhibitors of respiratory chain complexes and matrix enzymes. The biological ramifications of this model are tremendous, ranging from philosophical “mitochondrial theory of aging” to very practical and costly enterprises aimed at making mitochondria-targeted antioxidants that would “curb the production of ROS in mitochondria”. However, there are reported cases, in which the results of inhibitor analysis did not fit the “standard model”. We will discuss these cases in our presentation.