Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia
Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia
复制标题
DOI：
10.1016/j.neuint.2017.08.002
复制
发表时间：
2018-07-01
影响因子：
4.2
通讯作者：
Huang, Michael L-H
中科院分区：
文献类型：
--
作者：
Chiang, Shannon;Kalinowski, Danuta S.;Huang, Michael L-H
线粒体动态平衡对于维持健康的细胞功能和生存至关重要。线粒体功能障碍在神经退行性疾病中的有害作用最近在人类疾病中得到了强调，如帕金森氏症、阿尔茨海默氏症和亨廷顿病。Friedreich‘s共济失调(FA)是另一种神经退行性疾病，但也是心脏退行性疾病，线粒体功能障碍在疾病进展中起着关键作用。线粒体蛋白Frataxin的表达不足是FA的主要原因，FA导致整个细胞和线粒体铁代谢的不利变化。DYS-调节这些隔室中的铁代谢，导致线粒体基质中无机铁沉积的积累，这被认为加强了在FA中观察到的氧化损伤。因此，线粒体稳态的维持在神经退行性疾病的进展中是至关重要的，尤其是在FA中。在这篇综述中，将讨论重要的线粒体动态平衡过程及其在FA发病机制中的作用。这些包括线粒体铁加工、线粒体动力学(融合和分裂过程)、有丝分裂、线粒体生物发生、线粒体能量产生和钙代谢。(C)2017爱思唯尔有限公司。保留所有权利。
Mitochondrial homeostasis is essential for maintaining healthy cellular function and survival. The detrimental involvement of mitochondrial dysfunction in neuro-degenerative diseases has recently been highlighted in human conditions, such as Parkinson's, Alzheimer's and Huntington's disease. Friedreich's ataxia (FA) is another neuro-degenerative, but also cardio-degenerative condition, where mitochondrial dysfunction plays a crucial role in disease progression. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism. Dys-regulation of iron metabolism in these compartments, results in the accumulation of inorganic iron deposits in the mitochondrial matrix that is thought to potentiate oxidative damage observed in FA. Therefore, the maintenance of mitochondrial homeostasis is crucial in the progression of neuro-degenerative conditions, particularly in FA. In this review, vital mitochondrial homeostatic processes and their roles in FA pathogenesis will be discussed. These include mitochondrial iron processing, mitochondrial dynamics (fusion and fission processes), mitophagy, mitochondrial biogenesis, mitochondrial energy production and calcium metabolism. (C) 2017 Elsevier Ltd. All rights reserved.