Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signaling
Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signaling
复制标题
DOI：
10.1152/ajpheart.00699.2006
复制
发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Brookes, Paul S.
中科院分区：
文献类型：
--
作者：
Hoffman, David L.;Salter, Jason D.;Brookes, Paul S.
线粒体被认为在缺氧细胞信号传导中起重要作用。一个目前公认的信号范例是，线粒体产生的活性氧（ROS）增加缺氧。这是自相矛盾的，因为氧是ROS产生的底物。虽然分离的线粒体ROS产生的响应[O-2]之前已经检查，这样的调查没有应用严格的控制[O-2]在缺氧信号范围内。通过使用开放流呼吸测定法和荧光测定法，本研究确定了离体大鼠肝脏线粒体ROS生成对低至0.1 μ M的定义稳态[O-2]的响应。在状态4（静止）或状态3（ATP周转）条件下呼吸的线粒体中，在低[O-2]下总是观察到ROS生成减少。它的结论是，生化机制，以促进增加ROS的产生在细胞中的缺氧反应是不是固有的线粒体呼吸链单独，但可能涉及其他因素。缺氧细胞信号的影响进行了讨论。
Mitochondria are proposed to play an important role in hypoxic cell signaling. One currently accepted signaling paradigm is that the mitochondrial generation of reactive oxygen species (ROS) increases in hypoxia. This is paradoxical, because oxygen is a substrate for ROS generation. Although the response of isolated mitochondrial ROS generation to [O-2] has been examined previously, such investigations did not apply rigorous control over [O-2] within the hypoxic signaling range. With the use of open-flow respirometry and fluorimetry, the current study determined the response of isolated rat liver mitochondrial ROS generation to defined steady-state [O-2] as low as 0.1 mu M. In mitochondria respiring under state 4 (quiescent) or state 3 (ATP turnover) conditions, decreased ROS generation was always observed at low [O-2]. It is concluded that the biochemical mechanism to facilitate increased ROS generation in response to hypoxia in cells is not intrinsic to the mitochondrial respiratory chain alone but may involve other factors. The implications for hypoxic cell signaling are discussed.