Friedreich's ataxia is a multisystemic genetic disorder within the family of mitochondrial diseases that is characterized by reduced levels of the essential mitochondrial protein frataxin. Based on clinical evidence, the peripheral nervous system is affected early, neuronal dysfunction progresses towards the central nervous system, and other organs (such as heart and pancreas) are affected later. However, little attention has been given to the specific aspects of mitochondria function altered by frataxin depletion in the nervous system. For years, commonly accepted views on mitochondria dysfunction in Friedreich's ataxia stemmed from studies using non-neuronal systems and may not apply to neurons, which have their own bioenergetic needs and present a unique, extensive neurite network. Moreover, the basis of the selective neuronal vulnerability, which primarily affects large sensory neurons in the dorsal root ganglia, large principal neurons in the dentate nuclei of the cerebellum, and pyramidal neurons in the cerebral cortex, remains elusive. In order to identify potential misbeliefs in the field and highlight controversies, we reviewed current knowledge on frataxin expression in different tissues, discussed the molecular function of frataxin, and the consequences of its deficiency for mitochondria structural and functional properties, with a focus on the nervous system.

中文翻译：

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弗里德赖希共济失调神经元线粒体功能障碍。


弗里德赖希共济失调是线粒体疾病家族中的一种多系统遗传性疾病，其特征是必需的线粒体蛋白 frataxin 水平降低。根据临床证据，周围神经系统早期受到影响，神经元功能障碍向中枢神经系统发展，其他器官（例如心脏和胰腺）随后受到影响。然而，很少有人关注神经系统中 frataxin 消耗所改变的线粒体功能的具体方面。多年来，关于弗里德赖希共济失调线粒体功能障碍的普遍接受的观点源于使用非神经元系统的研究，可能不适用于神经元，因为神经元有自己的生物能需求并呈现独特的、广泛的神经突网络。此外，选择性神经元脆弱性的基础仍然难以捉摸，这种脆弱性主要影响背根神经节中的大感觉神经元、小脑齿状核中的大主要神经元和大脑皮层中的锥体神经元。为了识别该领域潜在的误解并强调争议，我们回顾了目前关于不同组织中 frataxin 表达的知识，讨论了 frataxin 的分子功能，以及其缺陷对线粒体结构和功能特性的后果，重点关注神经系统。