Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis.

TitleUbiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis.
Publication TypeJournal Article
Year of Publication2013
AuthorsMugoni, V, Postel, R, Catanzaro, V, De Luca, E, Turco, E, Digilio, G, Silengo, L, Murphy, MP, Medana, C, Stainier, DYR, Bakkers, J, Santoro, MM
Date Published2013 Jan 31
KeywordsAnimals, Dimethylallyltranstransferase, Endothelial Cells, Golgi Apparatus, Heart, Humans, Myocardium, Nitric Oxide Synthase Type III, Reactive Oxygen Species, Ubiquinone, Zebrafish, Zebrafish Proteins

Protection against oxidative damage caused by excessive reactive oxygen species (ROS) by an antioxidant network is essential for the health of tissues, especially in the cardiovascular system. Here, we identified a gene with important antioxidant features by analyzing a null allele of zebrafish ubiad1, called barolo (bar). bar mutants show specific cardiovascular failure due to oxidative stress and ROS-mediated cellular damage. Human UBIAD1 is a nonmitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Loss of UBIAD1 reduces the cytosolic pool of the antioxidant CoQ10 and leads to ROS-mediated lipid peroxidation in vascular cells. Surprisingly, inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, suggesting a crucial role for this enzyme and nonmitochondrial CoQ10 in NO signaling. These findings identify UBIAD1 as a nonmitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity.

Alternate JournalCell
Citation Key10.1016/j.cell.2013.01.013
PubMed ID23374346
PubMed Central IDPMC3574195
Grant ListGGP10195 / / Telethon / Italy
MC_U105663142 / / Medical Research Council / United Kingdom