MILD UNCOUPLING OF MITOCHONDRIA

Recently, it was proposed that the thyroid hormone-mediated uncoupling in mitochondria is involved in the cellular defence system against fr ee radicals (Skulachev V.P. (1996) Quart. Rev. Biophys. 29:169-202). T his phenomenon was named ''mild'' uncoupling. it was postulated to be a protein-mediated process controlled by several factors. The data rep orted during the past 40 years, pointing to the protein-mediated uncou pling mechanism in mitochondria, are reviewed in a context of hypothet ical properties of ''mild'' uncoupling. The mechanism of ''mild'' unco upling is suggested to be the following: (a) mitochondria possess prot ein(s) that regulate the proton permeability of inner mitochondrial me mbrane; (b) these proteins are regulated by binding of an unidentified low-molecular-weight endogenous compound with properties resembling t hose of the most active artificial uncouplers like FCCP and SF6847; (c ) the interaction of this compound with its target protein(s) is modul ated by a thyroid hormone in a positive (i.e. enhancing the proton per meability) way and by sex steroid hormones in a negative way; (e) endo genous fatty acids can attenuate the influence of both thyroid and ste roid hormones.