Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial
uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (~5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with th
e experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction
products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.
Apart from thyroid hormones, as the main hormonal regulators of obligatory thermogenesis, and catecholamines, as major hormonal regulators of facultative thermogenesis, production of heat in homeotherms can also be influenced by steroids. Generally, hormones can influence heat production by regulating the activity of various enzymes of oxidative metabolism, by modulating membrane protein carriers and other membrane or nuclear protein factors. Proton carriers in the inner mitochondrial membrane, known as uncoupling proteins, play the key role in heat dissipation to the detriment of the formation of energy-rich phosphates. In this minireview we have focused on the effects of steroids and thyroid hormones on heat production in brown adipose tissues and in skeletal muscles, with particular respect to their effect on uncoupling protein expression. Apart from hormonal steroids, dehydroepiandrosterone, an important precursor in the metabolic pathway leading to hormonal steroids which possess many, mostly beneficial effects on human health, modulates metabolic pathways which may lead to increased heat production. Recent studies demonstrate that 7-oxo-dehydroepiandrosterone, one of its 7-oxygenated metabolites, is even more effective than dehydroepiandrosterone. Recent findings of various actions of these steroids support the view that they may also participate in modulating thermogenic effects.