Brady Nathan R, Hamacher-Brady Anne, Westerhoff Hans V, Gottlieb Roberta A
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1651-65. doi: 10.1089/ars.2006.8.1651.
Once considered simply as the main source of ATP, mitochondria are now implicated in the control of many additional aspects of cell physiology, such as calcium signaling, and pathology, as in injury incurred on ischemia and subsequent reperfusion (I/R). Mitochondrial respiration is ordinarily accompanied by low-level ROS production, but they can respond to elevated ROS concentrations by increasing their own ROS production, a phenomenon termed ROS-induced ROS release (RIRR). Two modes of RIRR have been described. In the first mode of RIRR, enhanced ROS leads to mitochondrial depolarization via activation of the MPTP, yielding a short-lived burst of ROS originating from the mitochondrial electron transport chain (ETC). The second mode of RIRR is MPTP independent but is regulated by the mitochondrial benzodiazepine receptor (mBzR). Increased ROS in the mitochondrion triggers opening of the inner mitochondrial membrane anion channel (IMAC), resulting in a brief increase in ETC-derived ROS. Both modes of RIRR have been shown to transmit localized mitochondrial perturbations throughout the cardiac cell in the form of oscillations or waves but are kinetically distinct and may involve different ROS that serve as second messengers. In this review, we discuss the mechanisms of these different modes of RIRR.
线粒体曾经仅被视为三磷酸腺苷（ATP）的主要来源，如今它还参与细胞生理学的许多其他方面的调控，如钙信号传导，以及病理学过程，比如缺血再灌注（I/R）损伤。线粒体呼吸通常伴随着低水平的活性氧（ROS）生成，但它们可通过增加自身的ROS生成来应对升高的ROS浓度，这一现象被称为ROS诱导的ROS释放（RIRR）。RIRR已被描述有两种模式。在第一种RIRR模式中，增强的ROS通过线粒体通透性转换孔（MPTP）的激活导致线粒体去极化，产生源自线粒体电子传递链（ETC）的短暂ROS爆发。第二种RIRR模式不依赖MPTP，但受线粒体苯二氮䓬受体（mBzR）调控。线粒体中ROS的增加触发线粒体内膜阴离子通道（IMAC）开放，导致ETC衍生的ROS短暂增加。两种RIRR模式均已被证明能以振荡或波的形式将局部线粒体扰动传递至整个心肌细胞，但在动力学上有所不同，且可能涉及充当第二信使的不同ROS。在本综述中，我们讨论这些不同RIRR模式的机制。
