The coenzyme function of ubiquinone was subject of extensive studies in mitochondria since more than 40 years. The catalytic activity of ubiquinone (UQ) in electron transfer and proton translocation in cooperation with mitochondrial dehydrogenases and cytochromes contributes essentially to the bioenergetic activity of ATP synthesis. In the past two decades UQ was recognized to exert activities which differ from coenzyme functions in mitochondria. From extraction/reincorporation experiments B. Chance has drawn the conclusion that redox-cycling of mitochondrial ubiquinone supplies electrons for univalent reduction of dioxygen. The likelihood of O 2
.Οͺ release as normal byproduct of respiration was based on the existence of mitochondrial SOD and the fact that mitochondrial oxygen turnover accounts for more than 90% of total cellular oxygen consumption. Arguments disproving this concept are based on results obtained from a novel noninvasive, more sensitive detection method of activated oxygen species and novel experimental approaches, which threw light into the underlying mechanism of UQmediated oxygen activation. Single electrons for O 2
.Οͺ formation are exclusively provided by deprotonated ubisemiquinones. Impediment of redox-interaction with the bc 1 complex in mitochondria or the lack of stabilizing interactions with redox-partners are promotors of autoxidation. The latter accounts for autoxidation of antioxidant-derived ubisemiquinones in biomembranes, which do not recycle oxidized ubiquinols. Also O 2 .Οͺ -derived H 2 O 2 was found to interact with ubisemiquinones both in mitochondria and nonrecycling biomembranes when ubiquinol was active as antioxidant. The catalysis of reductive homolytic cleavage of H 2 O 2 , which contributes to HOΠΈ formation in biological systems was confirmed under defined chemical conditions in a homogenous reduction system. Apart from dioxygen and hydrogen peroxide we will provide evidence that also nitrite may chemically interact with the ubiquinol/bc 1 redox couple in mitochondria. The reaction product NO was reported elsewhere to be a significant bioregulator of the mitochondrial respiration and O 2 activation. Another novel finding documents the bioenergetic role of UQ in lysosomal proton intransport. A lysosomal chain of redox couples will be presented, which includes UQ and which requires oxygen as the terminal electron acceptor.