Brini Marisa
Department of Biochemistry of the National Research Council, University of Padova, 35121 Padova, Italy.
Cell Calcium. 2003 Oct-Nov;34(4-5):399-405. doi: 10.1016/s0143-4160(03)00145-3.
Over recent years, a renewed interest in mitochondria in the field of Ca(2+) signalling has highlighted their central role in regulating important physiological and pathological events in animal cells. Mitochondria take up calcium through an uptake pathway that, due to its low-Ca(2+) affinity, demands high local calcium concentrations to work. In different cell systems high-Ca(2+) concentration microdomains are generated, upon cell stimulation, in proximity of either plasma membrane or sarco/endoplasmic reticulum Ca(2+) channels. Mitochondrial Ca(2+) accumulation has a dual role, an universal one, which consists in satisfying energy demands by increasing the ATP production through the activation of mitochondrial enzymes, and a cell type specific one, which, through the modulation of the spatio-temporal dynamics of calcium signals, contributes to modulate specific cell functions. Recent work has revealed the central role of mitochondria dysfunction in determining both necrotic and apoptotic cell death. Evidence is also accumulating that suggests that alterations in mitochondrial function may act as predisposing factors in the pathogenesis of a number of neurodegenerative disorders. These include inherited disorders of the mitochondrial genome in which a defect in mitochondrial calcium accumulation has been shown to correlate with a defect in ATP production, thus suggesting a possible involvement of mitochondrial Ca(2+) dysfunction also for this group of diseases. This review analyses recent developments in the area of mitochondrial Ca(2+) signalling and attempts to summarise cell physiology and cell pathology aspects of the mitochondrial Ca(2+) transport machinery.
近年来，钙信号领域对线粒体的兴趣再度兴起，突显了其在调节动物细胞重要生理和病理事件中的核心作用。线粒体通过一种摄取途径摄取钙，由于其对钙的亲和力较低，需要高局部钙浓度才能发挥作用。在不同的细胞系统中，细胞受到刺激后，在质膜或肌浆网/内质网钙通道附近会产生高钙浓度微区。线粒体钙积累具有双重作用，一种是普遍作用，即通过激活线粒体酶增加ATP生成来满足能量需求；另一种是细胞类型特异性作用，即通过调节钙信号的时空动态，有助于调节特定的细胞功能。最近的研究揭示了线粒体功能障碍在决定坏死性和凋亡性细胞死亡中的核心作用。越来越多的证据表明，线粒体功能改变可能是许多神经退行性疾病发病机制中的易感因素。这些疾病包括线粒体基因组的遗传性疾病，其中线粒体钙积累缺陷已被证明与ATP生成缺陷相关，因此表明线粒体钙功能障碍可能也参与了这组疾病。本综述分析了线粒体钙信号领域的最新进展，并试图总结线粒体钙转运机制的细胞生理学和细胞病理学方面。
