Mitochondrial complex III is required for hypoxia-induced ROS production and gene transcription in yeast
Mitochondrial complex III is required for hypoxia-induced ROS production and gene transcription in yeast
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DOI：
10.1089/ars.2007.1708
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发表时间：
2007-09-01
影响因子：
6.6
通讯作者：
Schumacker, Paul T.
中科院分区：
文献类型：
--
作者：
Guzy, Robert D.;Mack, Matthew M.;Schumacker, Paul T.
为了生存，呼吸生物必须感知环境氧气水平的变化并做出反应。线粒体电子传递链（ETC）的复合物III通过其在缺氧期间增加活性氧（ROS）产生的能力参与哺乳动物的O-2传感途径。本研究测试了酵母中的复合物III是否也有助于缺氧期间的O-2传感。研究了线粒体DNA（p（0））、复合体III中的Rieske铁硫蛋白（Delta Rip 1）或负责辅酶Q生物合成的酶（Delta Coq 2）缺陷的菌株，以确定复合体III活性在对缺氧的转录应答中的重要性。复合物III功能的丧失消除了每个菌株中ROS的缺氧诱导的增加。北方分析鉴定了一组基因，这些基因在野生型中被缺氧激活，但在p（0）、Delta Rip 1或Delta Coq 2菌株中不被激活。缺乏转录因子Yap 1 p、Mga 2 p和Msn 2 p的酵母也缺乏基因转录的缺氧激活，这表明氧化还原调节在缺氧基因表达中的重要性。作者得出结论，ETC的复合物III是ROS产生和酵母中一组缺氧诱导基因表达所必需的。这些发现表明，线粒体O2传感机制在整个进化过程中是高度保守的。
To survive, respiring organisms must sense and respond to changes in environmental oxygen levels. Complex III of the mitochondrial electron transport chain (ETC) has been implicated in the O-2 sensing pathway in mammals through its ability to increase production of reactive oxygen species (ROS) during hypoxia. The present study tested whether Complex III in yeast also contributes to O-2 sensing during hypoxia. Strains deficient in mitochondrial DNA (p(0)), the Rieske iron-sulfur protein (Delta Rip1) in Complex III, or an enzyme responsible for coenzyme Q biosynthesis (Delta Coq2) were studied to determine the importance of Complex III activity in the transcriptional response to hypoxia. Loss of Complex III function abrogated the hypoxia-induced increase in ROS in each strain. Northern analysis identified a set of genes that are activated by hypoxia in wild-type but not in p(0), Delta Rip1, or Delta Coq2 strains. Yeast lacking the transcription factors Yap1p, Mga2p, and Msn2p were also deficient in hypoxic activation of gene transcription, suggesting the importance of redox regulation in hypoxic gene expression. The authors conclude that Complex III of the ETC is required for ROS production and for expression of a group of hypoxia-inducible genes in yeast. These findings indicate that the mitochondrial O2 sensing mechanism is highly conserved throughout evolution.