The existence and significance of redox-cycling ubiquinone in lysosomes.
Ubiquinone is inhomogeneously 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 proteases. 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 reported to exist 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 flavin 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 regulating acidification of the lysosomal matrix. The role of the proton-pumping redox chain has to be elucidated.
Nohl
H
H
Institute of Pharmacology and Toxicology, Veterinary University Vienna, Veterinärplatz 1, A-1210 Vienna, Austria.
Gille
L
L
D000818:Animals; D003497:Cyclic N-Oxides / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011522:Protons; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013113:Spin Labels; D014451:Ubiquinone / Q000378:metabolism*; D014475:Uncoupling Agents / Q000494:pharmacology
D003497:Cyclic N-Oxides; D003573:Cytochrome b Group; D004791:Enzyme Inhibitors; D011522:Protons; D013113:Spin Labels; D014475:Uncoupling Agents; D012402:Rotenone; D009243:NAD; D014451:Ubiquinone; D005182:Flavin-Adenine Dinucleotide; C015527:4-amino-TEMPO; D010100:Oxygen; D008797:Metyrapone