title: The bifunctional activity of ubiquinone in lysosomal membranes.
abstract: Ubiquinone is inhomogenously distributed in subcellular biomembranes. Apart from mitochondria where ubiquinone was demonstrated to exert bioenergetic and pathophysiological functions, unusually high levels of ubiquinone were also reported to exist in Golgi vesicles and lysosomes. In lysosomes the interior differs from other organelles by the low pH-value, which is important not only to arrest proteins but also to ensure optimal activity of hydrolytic enzymes. Since redox-cycling of ubiquinone is associated with the acceptance and release of protons, we assumed that ubiquinone is a part of a redox chain contributing to unilateral proton distribution. A similar function of ubiquinone was earlier suggested by Crane to operate in Golgi vesicles. Support for the involvement of ubiquinone in a presumed couple of redox-carriers came from our observation that almost 70% of total lysosomal ubiquinone was in the divalently reduced state. Further reduction was seen in the presence of external NADH. Analysis of the components involved in the transfer of reducing equivalents from cytosolic NADH to ubiquinone revealed the existence of a FAD-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 regulating acidification of the lysosomal matrix. In contrast to mitochondrial respiration, oxygen was only trivalently reduced, giving rise to the release of HO*-radicals. The role of this novel proton-pumping redox chain and the significance of the associated ROS formation has to be elucidated.
authors.affiliation: Institute of Pharmacology and Toxicology, Veterinary University Vienna, Austria. Hans.Nohl@vu-wien.ac.at
authors.forename: Hans
authors.initials: H
authors.lastname: Nohl
authors.forename: Lars
authors.initials: L
authors.lastname: Gille
mesh_terms: D000818:Animals; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000648:ultrastructure; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D014451:Ubiquinone / Q000378:metabolism*
chemical_list: D009243:NAD; D014451:Ubiquinone; D010100:Oxygen