To proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2 as well as of one-electron O2 reductants such as These two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of , and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2 and the O2 reductants when phosphorylating respiration fails to do this job due to lack of ADP.

In particular, it is proposed that some increase in the H+ leak of mitochondrial membrane in State 4 lowers , stimulates O2 consumption and decreases the level of which otherwise accumulates and serves as one-electron O2 reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.