Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options remain limited. Over the past two decades, there is growing evidence that patients with mitochondrial disorders have nitric oxide (NO) deficiency due to limited availability of NO substrates, arginine and citrulline; decreased activity of nitric oxide synthase (NOS); and NO sequestration. Studies evaluating the use of arginine in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting with stroke-like episodes showed symptomatic improvement after acute administration as well as reduction in frequency and severity of stroke-like episodes following chronic use. Citrulline, another NO precursor, was shown through stable isotope studies to result in a greater increase in NO synthesis. Recent studies showed positive response of arginine and citrulline in other mitochondrial disorders besides MELAS. Randomized-controlled studies with larger number of patients are warranted to better understand the role of NO deficiency in mitochondrial disorders and the efficacy of NO precursors as treatment modalities in these disorders.

中文翻译：

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线粒体疾病中的一氧化氮缺乏：精氨酸和瓜氨酸的效用

线粒体疾病代表了越来越多的临床异质性疾病，这些疾病与线粒体功能障碍和多系统表现相关。尽管对线粒体疾病的潜在病理生理基础有了更好的了解，但治疗选择仍然有限。在过去的二十年里，越来越多的证据表明，由于 NO 底物、精氨酸和瓜氨酸的可用性有限，线粒体疾病患者存在一氧化氮 (NO) 缺乏症；一氧化氮合酶 (NOS) 活性降低；并且没有封存。评估精氨酸在线粒体肌病、脑病、乳酸性酸中毒、和中风样发作（MELAS）在急性给药后表现出症状改善，以及长期使用后中风样发作的频率和严重程度降低。瓜氨酸是另一种 NO 前体，通过稳定同位素研究显示，NO 合成增加更多。最近的研究表明精氨酸和瓜氨酸在除 MELAS 之外的其他线粒体疾病中也有积极反应。需要对更多患者进行随机对照研究，以更好地了解 NO 缺乏在线粒体疾病中的作用以及 NO 前体作为这些疾病治疗方式的疗效。通过稳定同位素研究表明，NO 合成增加更多。最近的研究表明精氨酸和瓜氨酸在除 MELAS 之外的其他线粒体疾病中也有积极反应。需要对更多患者进行随机对照研究，以更好地了解 NO 缺乏在线粒体疾病中的作用以及 NO 前体作为这些疾病治疗方式的疗效。通过稳定同位素研究表明，NO 合成增加更多。最近的研究表明精氨酸和瓜氨酸在除 MELAS 之外的其他线粒体疾病中也有积极反应。需要对更多患者进行随机对照研究，以更好地了解 NO 缺乏在线粒体疾病中的作用以及 NO 前体作为这些疾病治疗方式的疗效。