Mitochondrial Free Radical Leak

It is frequently assumed that mitochondrial ROS production is a direct function of mitochondrial O2 consumption. While this is sometimes true (Ku et al., 1993), in other situations, including comparisons between birds and mammals or caloric restriction (Barja, 2004), this is not the case. A well-known example is the transition from state 4 to state 3, during which mitochondrial O2 consumption increases strongly but ROS production decreases or is even totally abolished. In this last case ROS production per unit oxygen consumption decreases acutely during the energy transition. In other words, during state 3 mitochondria are more efficient than in state 4, avoiding ROS generation per unit electron flow in the respiratory chain, which is clearly adaptive. This can be quantified by measuring the ''free radical leak'': the fraction (%) of electrons out of sequence which reduce oxygen to ROS in the mitochondrial respiratory chain

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