Office of Dietary Supplements, National Institutes of Health, Bethesda, Maryland 20852, USA; email:
Division of Cancer Biology, National Cancer Institute, Rockville, Maryland 20850, USA; email:
Annu Rev Pathol. 2018 Jan 24;13:163-191. doi: 10.1146/annurev-pathol-020117-043644. Epub 2017 Nov 3.
Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe, often lethal, conditions. Inborn errors of OXPHOS function are termed primary mitochondrial disorders (PMDs), and the use of nutritional interventions is routine in their supportive management. However, detailed mechanistic understanding and evidence for efficacy and safety of these interventions are limited. Preclinical cellular and animal model systems are important tools to investigate PMD metabolic mechanisms and therapeutic strategies. This review assesses the mechanistic rationale and experimental evidence for nutritional interventions commonly used in PMDs, including micronutrients, metabolic agents, signaling modifiers, and dietary regulation, while highlighting important knowledge gaps and impediments for randomized controlled trials. Cellular and animal model systems that recapitulate mutations and clinical manifestations of specific PMDs are evaluated for their potential in determining pathological mechanisms, elucidating therapeutic health outcomes, and investigating the value of nutritional interventions for mitochondrial disease conditions.
由氧化磷酸化（OXPHOS）缺陷引起的多系统代谢紊乱是严重的，通常是致命的疾病。OXPHOS 功能的先天性错误被称为原发性线粒体疾病（PMD），在其支持性管理中，营养干预是常规的。然而，这些干预措施的详细机制理解以及疗效和安全性的证据是有限的。临床前细胞和动物模型系统是研究 PMD 代谢机制和治疗策略的重要工具。本综述评估了 PMD 中常用的营养干预措施的机制原理和实验证据，包括微量营养素、代谢剂、信号调节剂和饮食调节，同时强调了随机对照试验的重要知识差距和障碍。评估了再现特定 PMD 突变和临床表现的细胞和动物模型系统，以确定病理机制、阐明治疗健康结果，并研究营养干预对线粒体疾病的价值。
