Mitochondrial Ca(2+) and neurodegeneration.
Mitochondrial Ca(2+) and neurodegeneration.
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DOI：
10.1016/j.ceca.2012.04.015
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发表时间：
2012-07
期刊：
影响因子：
4
通讯作者：
Brini M
中科院分区：
文献类型：
--
作者：
Calì T;Ottolini D;Brini M
线粒体对于确保许多基本的生理过程是必不可少的，例如细胞能量、氧化还原平衡、Ca2+信号传导的调节和重要的生物合成途径。它们还通过参与细胞凋亡途径来控制细胞命运。细胞内线粒体的形状、体积、数量和分布受到严格控制。这些参数的调节对线粒体功能有影响，特别是在中枢神经系统中，线粒体的运输对其战略性细胞内分布至关重要，可能是根据局部能量需求。因此，维持健康的线粒体群体对于避免它们调节的过程受损是至关重要的：为此，细胞已经开发了涉及复杂的质量控制系统的机制，以去除受损的线粒体或更新它们。这些过程的缺陷损害线粒体功能并导致细胞功能紊乱，即，一种疾病。考虑到线粒体在所有细胞中的标准作用，可以预期它们的功能障碍将在所有组织中引起类似的缺陷。然而，受损的线粒体功能在多细胞生物体中具有多效性效应，导致多种病理状况，从心脏和脑缺血到骨骼肌肌病到神经退行性疾病。在这篇综述中，我们将重点关注神经退行性疾病中线粒体（和细胞）紊乱和Ca2+失调之间的关系，强调遗传模型中获得的证据。常见的模式，即承认混乱的Ca2+和能量控制作为一个致病因素，已被确定：在理解Ca2+稳态的分子调控的进展，以及在神经系统疾病中，它可能成为扰动的方式，可能会导致调节神经元Ca2+信号的治疗策略的发展。
Mitochondria are essential for ensuring numerous fundamental physiological processes such as cellular energy, redox balance, modulation of Ca2+ signaling and important biosynthetic pathways. They also govern the cell fate by participating in the apoptosis pathway. The mitochondrial shape, volume, number and distribution within the cells are strictly controlled. The regulation of these parameters has an impact on mitochondrial function, especially in the central nervous system, where trafficking of mitochondria is critical to their strategic intracellular distribution, presumably according to local energy demands. Thus, the maintenance of a healthy mitochondrial population is essential to avoid the impairment of the processes they regulate: for this purpose, cells have developed mechanisms involving a complex system of quality control to remove damaged mitochondria, or to renew them. Defects of these processes impair mitochondrial function and lead to disordered cell function, i.e., to a disease condition. Given the standard role of mitochondria in all cells, it might be expected that their dysfunction would give rise to similar defects in all tissues. However, damaged mitochondrial function has pleiotropic effects in multicellular organisms, resulting in diverse pathological conditions, ranging from cardiac and brain ischemia, to skeletal muscle myopathies to neurodegenerative diseases. In this review, we will focus on the relationship between mitochondrial (and cellular) derangements and Ca2+ dysregulation in neurodegenerative diseases, emphasizing the evidence obtained in genetic models. Common patterns, that recognize the derangement of Ca2+ and energy control as a causative factor, have been identified: advances in the understanding of the molecular regulation of Ca2+ homeostasis, and on the ways in which it could become perturbed in neurological disorders, may lead to the development of therapeutic strategies that modulate neuronal Ca2+ signaling.
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