The multiple functions of coenzyme Q

The coenzyme function of ubiquinone was subject of extensive studies in mit ochondria since more than 40 years. The catalytic activity of ubiquinone (U Q) in electron transfer and proton translocation in cooperation with mitoch ondrial dehydrogenases and cytochromes contributes essentially to the bioen ergetic activity of ATP synthesis. In the past two decades UQ was recognize d to exert activities which differ from coenzyme functions in mitochondria. From extraction/reincorporation experiments B. Chance has drawn the conclu sion that redox-cycling of mitochondrial ubiquinone supplies electrons for univalent reduction of dioxygen. The likelihood of O-2(-) release as normal byproduct of respiration was based on the existence of mitochondrial SOD a nd the fact that mitochondrial oxygen turnover accounts for more than 90% o f total cellular oxygen consumption. Arguments disproving this concept are based on results obtained from a novel noninvasive, more sensitive detectio n method of activated oxygen species and novel experimental approaches, whi ch threw light into the underlying mechanism of UQ-mediated oxygen activati on. Single electrons for O-2(-) formation are exclusively provided by depro tonated ubisemiquinones. Impediment of redox-interaction with the bc(1) com plex in mitochondria or the lack of stabilizing interactions with redox-par tners are promoters of autoxidation. The latter accounts for autoxidation o f antioxidant-derived ubisemiquinones in biomembranes. which do not recycle oxidized ubiquinols. Also O-2(-) derived H2O2 was found to interact with u bisemiquinones both in mitochondria and nonrecycling biomembranes when ubiq uinol was active as antioxidant, The catalysis of reductive homolytic cleav age of H2O2, which contributes to HO . formation in biological systems was confirmed under defined chemical conditions in a homogenous reduction syste m. 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 sig nificant bioregulator of the mitochondrial respiration and O-2 activation. Another novel finding documents the bioenergetic role of UQ in lysosomal pr oton intransport. A lysosomal chain of redox couples will be presented, whi ch includes UQ and which requires oxygen as the terminal electron acceptor. (C) 2001 Academic Press.