Ubiad1 是一种抗氧化酶，通过 CoQ10 的合成来调节 eNOS 的活性。
Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis.
机构信息
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
出版信息
Cell. 2013 Jan 31;152(3):504-18. doi: 10.1016/j.cell.2013.01.013.
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.
抗氧化网络对活性氧（ROS）引起的氧化损伤的保护对组织的健康至关重要，特别是在心血管系统中。在这里，我们通过分析斑马鱼 ubiad1 的一个无效等位基因（称为 barolo，bar），鉴定出一个具有重要抗氧化特性的基因。bar 突变体由于氧化应激和 ROS 介导的细胞损伤而表现出特定的心血管衰竭。人类 UBIAD1 是非线粒体的prenyltransferase，在高尔基体膜隔室中合成 CoQ10。UBIAD1 的缺失会减少细胞溶质中抗氧化 CoQ10 的池，导致血管细胞中 ROS 介导的脂质过氧化。令人惊讶的是，eNOS 的抑制可预防 Ubiad1 依赖性心血管氧化损伤，表明该酶和非线粒体 CoQ10 在 NO 信号转导中起关键作用。这些发现确定了 UBIAD1 作为一种非线粒体 CoQ10 形成酶，通过调节 eNOS 活性具有特定的心血管保护功能。
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