Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia.
Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, 2006, Australia.
Neurochem Int. 2018 Jul;117:35-48. doi: 10.1016/j.neuint.2017.08.002. Epub 2017 Aug 4.
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.
线粒体动态平衡对于维持细胞的健康功能和存活至关重要。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，如帕金森病、阿尔茨海默病和亨廷顿病。弗里德里希共济失调（Friedreich's ataxia，FA）是另一种神经退行性疾病，也是心血管退行性疾病，其中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，这导致整个细胞和线粒体铁代谢的不利改变。这些隔室中铁代谢的失调导致无机铁沉积物在线粒体基质中的积累，这被认为增强了 FA 中观察到的氧化损伤。因此，维持线粒体动态平衡对于神经退行性疾病的进展至关重要，特别是在 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。这些过程包括线粒体铁处理、线粒体动力学（融合和裂变过程）、线粒体自噬、线粒体生物发生、线粒体能量产生和钙代谢。
