Camello-Almaraz Cristina, Gomez-Pinilla Pedro J, Pozo Maria J, Camello Pedro J
Dept. of Physiology, University of Extremadura, 10071 Cáceres, Spain.
Am J Physiol Cell Physiol. 2006 Nov;291(5):C1082-8. doi: 10.1152/ajpcell.00217.2006. Epub 2006 Jun 7.
Mitochondria are an important source of reactive oxygen species (ROS) formed as a side product of oxidative phosphorylation. The main sites of oxidant production are complex I and complex III, where electrons flowing from reduced substrates are occasionally transferred to oxygen to form superoxide anion and derived products. These highly reactive compounds have a well-known role in pathological states and in some cellular responses. However, although their link with Ca(2+) is well studied in cell death, it has been hardly investigated in normal cytosolic calcium concentration (Ca(2+)) signals. Several Ca(2+) transport systems are modulated by oxidation. Oxidation increases the activity of inositol 1,4,5-trisphosphate and ryanodine receptors, the main channels releasing Ca(2+) from intracellular stores in response to cellular stimulation. On the other hand, mitochondria are known to control Ca(2+) signals by Ca(2+) uptake and release during cytosolic calcium mobilization, specially in mitochondria situated close to Ca(2+) release channels. Mitochondrial inhibitors modify calcium signals in numerous cell types, including oscillations evoked by physiological stimulus. Although these inhibitors reduce mitochondrial Ca(2+) uptake, they also impair ROS production in several systems. In keeping with this effect, recent reports show that antioxidants or oxidant scavengers also inhibit physiological calcium signals. Furthermore, there is evidence that mitochondria generate ROS in response to cell stimulation, an effect suppressed by mitochondrial inhibitors that simultaneously block Ca(2+) signals. Together, the data reviewed here indicate that Ca(2+)-mobilizing stimulus generates mitochondrial ROS, which, in turn, facilitate Ca(2+) signals, a new aspect in the biology of mitochondria. Finally, the potential implications for biological modeling are discussed.
线粒体是氧化磷酸化过程中作为副产物形成的活性氧（ROS）的重要来源。氧化剂产生的主要部位是复合体I和复合体III，从还原底物流出的电子偶尔会转移到氧上，形成超氧阴离子及其衍生产物。这些高反应性化合物在病理状态和一些细胞反应中具有众所周知的作用。然而，尽管它们与Ca(2+)的联系在细胞死亡中得到了充分研究，但在正常胞质钙浓度（[Ca(2+)]i）信号中却几乎没有被研究过。几种Ca(2+)转运系统受氧化作用调节。氧化增加了肌醇1,4,5-三磷酸和兰尼碱受体的活性，这是响应细胞刺激从细胞内储存释放Ca(2+)的主要通道。另一方面，已知线粒体在胞质钙动员期间通过摄取和释放Ca(2+)来控制[Ca(2+)]i信号，特别是在靠近Ca(2+)释放通道的线粒体中。线粒体抑制剂会改变多种细胞类型中的钙信号，包括生理刺激引起的振荡。尽管这些抑制剂会减少线粒体Ca(2+)摄取，但它们也会损害多个系统中的ROS产生。与此效应一致，最近的报告表明抗氧化剂或氧化剂清除剂也会抑制生理钙信号。此外，有证据表明线粒体响应细胞刺激产生活性氧，这种效应被同时阻断[Ca(2+)]i信号的线粒体抑制剂所抑制。总之，这里综述的数据表明，Ca(2+)动员刺激产生活线粒体ROS，进而促进[Ca(2+)]i信号，这是线粒体生物学中的一个新方面。最后，讨论了其对生物学建模的潜在影响。
