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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents



ID: 682177.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis
Authors:Mugoni, V.; Postel, R.; Catanzaro, V.; De Luca, E.; Turco, E.; Digilio, G.; Silengo, L.; Murphy, M. P.; Medana, C.; Stainier, D. Y.; Bakkers, J.; Santoro, M. M.
Date of Publication (YYYY-MM-DD):2013-01-31
Journal Abbrev.:Cell
Volume:152
Issue / Number:3
Start Page:504
End Page:518
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals; Dimethylallyltranstransferase/genetics/*metabolism; Endothelial Cells/*metabolism; Golgi Apparatus/metabolism; Heart/embryology; Humans; Myocardium/cytology; Nitric Oxide Synthase Type III/*metabolism; Reactive Oxygen Species/metabolism; Ubiquinone/*analogs & derivatives/genetics; Zebrafish/embryology/*metabolism; Zebrafish Proteins/genetics/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1097-4172 (Electronic) 0092-8674 (Linking) %R 10.1016/j.cell.2013.01.013
URL:http://www.ncbi.nlm.nih.gov/pubmed/23374346
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