Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, PQ, H3G 1Y6, Canada.
Free Radic Biol Med. 2011 Dec 15;51(12):2243-8. doi: 10.1016/j.freeradbiomed.2011.08.036. Epub 2011 Sep 10.
Reactive oxygen species (ROS) play an important role in normal signaling events and excessive ROS are associated with many pathological conditions. The amount of ROS in cells is dependent on both the production of ROS by the mitochondrial electron transport chain and their removal by ROS-detoxifying enzymes. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a master regulator of mitochondrial functions and a key regulator of the ROS-detoxifying program. However, the impact of PGC-1α on the topology and rate of superoxide production by the mitochondrial electron transport chain is not known. We report here, using mitochondria from muscle creatine kinase-PGC-1α transgenic mice, that PGC-1α does not affect the topology of ROS production, but increases the capacity of complexes I and III to generate ROS. These changes are associated with increased mitochondrial respiration and content of respiratory chain complexes. When normalizing ROS production to mitochondrial respiration, we find that PGC-1α preserves the percentage of free radical leak by the electron transport chain. Together, these data demonstrate that PGC-1α regulates the intrinsic properties of mitochondria in such a way as to preserve a tight coupling between mitochondrial respiration and ROS production.
活性氧（ROS）在正常信号事件中发挥重要作用，过量的 ROS 与许多病理状况有关。细胞内 ROS 的含量既取决于线粒体电子传递链产生的 ROS，也取决于 ROS 解毒酶清除 ROS 的能力。过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）是线粒体功能的主要调节因子，也是 ROS 解毒程序的关键调节因子。然而，PGC-1α 对线粒体电子传递链中超氧化物产生的拓扑结构和速率的影响尚不清楚。我们在这里报告，使用来自肌肉肌酸激酶-PGC-1α 转基因小鼠的线粒体，PGC-1α 不影响 ROS 产生的拓扑结构，但增加了复合物 I 和 III 产生 ROS 的能力。这些变化与线粒体呼吸和呼吸链复合物含量的增加有关。当将 ROS 产生与线粒体呼吸归一化时，我们发现 PGC-1α 可以保持电子传递链自由基泄漏的百分比。总之，这些数据表明 PGC-1α 以一种方式调节线粒体的固有特性，从而在线粒体呼吸和 ROS 产生之间保持紧密的偶联。
