Laboratorio de Enfermedades Raras: Mitocondriales y Neuromusculares, Instituto de Investigación Hospital Universitario 12 de Octubre (i+12), Madrid, Spain.
Free Radic Biol Med. 2012 Aug 1;53(3):595-609. doi: 10.1016/j.freeradbiomed.2012.05.009. Epub 2012 May 14.
For decades mitochondria have been considered static round-shaped organelles in charge of energy production. In contrast, they are highly dynamic cellular components that undergo continuous cycles of fusion and fission influenced, for instance, by oxidative stress, cellular energy requirements, or the cell cycle state. New important functions beyond energy production have been attributed to mitochondria, such as the regulation of cell survival, because of their role in the modulation of apoptosis, autophagy, and aging. Primary mitochondrial diseases due to mutations in genes involved in these new mitochondrial functions and the implication of mitochondrial dysfunction in multifactorial human pathologies such as cancer, Alzheimer and Parkinson diseases, or diabetes has been demonstrated. Therefore, mitochondria are set at a central point of the equilibrium between health and disease, and a better understanding of mitochondrial functions will open new fields for exploring the roles of these mitochondrial pathways in human pathologies. This review dissects the relationships between activity and assembly defects of the mitochondrial respiratory chain, oxidative damage, and alterations in mitochondrial dynamics, with special focus on their implications for neurodegeneration.
几十年来，线粒体一直被认为是负责能量产生的静态圆形细胞器。相比之下，它们是高度动态的细胞成分，经历着融合和裂变的连续循环，这些循环受到氧化应激、细胞能量需求或细胞周期状态等因素的影响。除了能量产生之外，线粒体还具有新的重要功能，如调节细胞存活，因为它们在调节细胞凋亡、自噬和衰老方面发挥作用。已经证明，由于涉及这些新线粒体功能的基因突变以及线粒体功能障碍在癌症、阿尔茨海默病和帕金森病或糖尿病等多因素人类病理学中的作用，原发性线粒体疾病的发生与这些功能有关。因此，线粒体处于健康与疾病平衡的中心位置，对线粒体功能的更好理解将为探索这些线粒体途径在人类病理学中的作用开辟新的领域。这篇综述剖析了线粒体呼吸链的活性和组装缺陷、氧化损伤以及线粒体动力学改变之间的关系，特别关注它们对神经退行性变的影响。
