Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Free Radic Biol Med. 2011 Oct 1;51(7):1289-301. doi: 10.1016/j.freeradbiomed.2011.06.033. Epub 2011 Jul 6.
Reactive oxygen species (ROS) play an important role in physiological and pathological processes. In recent years, a feed-forward regulation of the ROS sources has been reported. The interactions between the main cellular sources of ROS, such as mitochondria and NADPH oxidases, however, remain obscure. This work summarizes the latest findings on the role of cross talk between mitochondria and NADPH oxidases in pathophysiological processes. Mitochondria have the highest levels of antioxidants in the cell and play an important role in the maintenance of cellular redox status, thereby acting as an ROS and redox sink and limiting NADPH oxidase activity. Mitochondria, however, are not only a target for ROS produced by NADPH oxidase but also a significant source of ROS, which under certain conditions may stimulate NADPH oxidases. This cross talk between mitochondria and NADPH oxidases, therefore, may represent a feed-forward vicious cycle of ROS production, which can be pharmacologically targeted under conditions of oxidative stress. It has been demonstrated that mitochondria-targeted antioxidants break this vicious cycle, inhibiting ROS production by mitochondria and reducing NADPH oxidase activity. This may provide a novel strategy for treatment of many pathological conditions including aging, atherosclerosis, diabetes, hypertension, and degenerative neurological disorders in which mitochondrial oxidative stress seems to play a role. It is conceivable that the use of mitochondria-targeted treatments would be effective in these conditions.
活性氧 (ROS) 在生理和病理过程中发挥着重要作用。近年来，人们报道了 ROS 来源的前馈调节。然而，ROS 的主要细胞来源（如线粒体和 NADPH 氧化酶）之间的相互作用仍不清楚。本文总结了线粒体和 NADPH 氧化酶之间相互作用在病理生理过程中的作用的最新发现。线粒体是细胞内抗氧化剂水平最高的细胞器，在维持细胞氧化还原状态方面发挥着重要作用，因此充当 ROS 和氧化还原的汇，并限制 NADPH 氧化酶的活性。然而，线粒体不仅是 NADPH 氧化酶产生的 ROS 的靶标，也是 ROS 的重要来源，在某些条件下，ROS 可能会刺激 NADPH 氧化酶。因此，线粒体和 NADPH 氧化酶之间的这种相互作用可能代表 ROS 产生的前馈恶性循环，在氧化应激条件下可以通过药理学方法靶向该循环。已经证明，靶向线粒体的抗氧化剂可以打破这种恶性循环，抑制线粒体产生 ROS，并降低 NADPH 氧化酶的活性。这可能为包括衰老、动脉粥样硬化、糖尿病、高血压和退行性神经疾病在内的许多病理状况提供一种新的治疗策略，其中线粒体氧化应激似乎发挥作用。可以想象，在这些情况下，使用靶向线粒体的治疗方法将是有效的。
