Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, Gower Street, London WC1E 6BT, UK.
Essays Biochem. 2010;47:115-37. doi: 10.1042/bse0470115.
The chapters throughout this volume illustrate the many contributions of mitochondria to the maintenance of normal cell and tissue function, experienced as the health of the individual. Mitochondria are essential for maintaining aspects of physiology as fundamental as cellular energy balance, the modulation of calcium signalling, in defining cellular redox balance, and they house significant biosynthetic pathways. Mitochondrial numbers and volume within cells are regulated and have an impact on their functional roles, while, especially in the CNS (central nervous system), mitochondrial trafficking is critical to ensure the cellular distribution and strategic localization of mitochondria, presumably driven by local energy demand. Maintenance of a healthy mitochondrial population involves a complex system of quality control, involving degrading misfolded proteins, while damaged mitochondria are renewed by fusion or removed by autophagy. It seems evident that mechanisms that impair any of these processes will impair mitochondrial function and cell signalling pathways, leading to disordered cell function which manifests as disease. As gatekeepers of cell life and cell death, mitochondria regulate both apoptotic and necrotic cell death, and so at its most extreme, disturbances involving these pathways may trigger untimely cell death. Conversely, the lack of appropriate cell death can lead to inappropriate tissue growth and development of tumours, which are also characterized by altered mitochondrial metabolism. The centrality of mitochondrial dysfunction to a surprisingly wide range of major human diseases is slowly becoming recognized, bringing with it the prospect of novel therapeutic approaches to treat a multitude of unpleasant and pervasive diseases.
本卷各章说明了线粒体对维持正常细胞和组织功能的许多贡献，这些贡献被视为个体的健康。线粒体对于维持细胞能量平衡、钙信号调节、细胞氧化还原平衡等基本生理过程至关重要，同时还拥有重要的生物合成途径。线粒体的数量和体积在细胞内受到调节，这对它们的功能角色有影响，而在线粒体在细胞内的分布和定位中起着关键作用的中枢神经系统（CNS）中，线粒体的运输对于确保线粒体的分布和定位至关重要，这可能是由局部能量需求驱动的。维持健康的线粒体群体涉及一个复杂的质量控制系统，包括降解错误折叠的蛋白质，而受损的线粒体通过融合或自噬来更新。很明显，任何损害这些过程的机制都会损害线粒体功能和细胞信号通路，导致细胞功能紊乱，表现为疾病。作为细胞生死的守门员，线粒体调节细胞凋亡和细胞坏死，因此在最极端的情况下，这些途径的紊乱可能会引发过早的细胞死亡。相反，适当的细胞死亡的缺失会导致组织过度生长和肿瘤的形成，而肿瘤的特征也是线粒体代谢的改变。线粒体功能障碍与一系列令人惊讶的人类重大疾病密切相关，这一发现为治疗多种令人不快和普遍存在的疾病带来了新的治疗方法的前景。
