The existence and significance of redox-cycling ubiquinone in lysosomes

Ubiquinone is inhomogeneously distributed in subcellular biomembranes. Apar t from mitochondria, where ubiquinone was demonstrated to exert bioenergeti c and pathophysiological functions, unusually high levels of ubiquinone wer e also reported to exist in Golgi vesicles and lysosomes. In lysosomes the interior differs from other organelles by the low pH value which is importa nt not only to arrest proteins but also to ensure optimal activity of prote ases. Since redox cycling of ubiquinone is associated with the acceptance a nd release of protons, we assumed that ubiquinone is a part of a redox chai n contributing to unilateral proton distribution. A similar function of ubi quinone was earlier reported to exist in Golgi vesicles. Support for the in volvement of ubiquinone in a presumed couple of redox carriers came from ou r observation that almost 70% of total lysosomal ubiquinone was in the diva lently reduced state. Further reduction was seen in the presence of externa l NADH. Analysis of the components involved in the transfer of reducing equ ivalents from cytosolic NADH to ubiquinone revealed the existence of a flav in adenine dinucleotide-containing NADH dehydrogenase. The latter was found to reduce ubiquinone by means of a b-type cytochrome. Proton translocation into the interior was linked to the activity of the novel lysosomal redox chain. Oxygen was found to be the terminal electron acceptor thereby also r egulating acidification of the lysosomal matrix. The role of the proton-pum ping redox chain has to be elucidated.