Abstract：
UNASSIGNED: Primary mitochondrial diseases (PMDs) are rare genetic disorders resulting from mutations in genes crucial for effective oxidative phosphorylation (OXPHOS) that can affect mitochondrial function. In this review, we examine the bioenergetic alterations and oxidative stress observed in cellular models of primary mitochondrial diseases (PMDs), shedding light on the intricate complexity between mitochondrial dysfunction and cellular pathology. We explore the diverse cellular models utilized to study PMDs, including patient-derived fibroblasts, induced pluripotent stem cells (iPSCs) and cybrids. Moreover, we also emphasize the connection between oxidative stress and neuroinflammation.
UNASSIGNED: The central nervous system (CNS) is particularly vulnerable to mitochondrial dysfunction due to its dependence on aerobic metabolism and the correct functioning of OXPHOS. Similar to other neurodegenerative diseases affecting the CNS, individuals with PMDs exhibit several neuroinflammatory hallmarks alongside neurodegeneration, a pattern also extensively observed in mouse models of mitochondrial diseases. Based on histopathological analysis of postmortem human brain tissue and findings in mouse models of PMDs, we posit that neuroinflammation is not merely a consequence of neurodegeneration but a potential pathogenic mechanism for disease progression that deserves further investigation. This recognition may pave the way for novel therapeutic strategies for this group of devastating diseases that currently lack effective treatments.
CONCLUSIONS: In summary, this review provides a comprehensive overview of bioenergetic alterations and redox imbalance in cellular models of PMDs while underscoring the significance of neuroinflammation as a potential driver in disease progression.
UNASSIGNED: The central nervous system (CNS) is particularly vulnerable to mitochondrial dysfunction due to its dependence on aerobic metabolism and the correct functioning of OXPHOS. Similar to other neurodegenerative diseases affecting the CNS, individuals with PMDs exhibit several neuroinflammatory hallmarks alongside neurodegeneration, a pattern also extensively observed in mouse models of mitochondrial diseases. Based on histopathological analysis of postmortem human brain tissue and findings in mouse models of PMDs, we posit that neuroinflammation is not merely a consequence of neurodegeneration but a potential pathogenic mechanism for disease progression that deserves further investigation. This recognition may pave the way for novel therapeutic strategies for this group of devastating diseases that currently lack effective treatments.
CONCLUSIONS: In summary, this review provides a comprehensive overview of bioenergetic alterations and redox imbalance in cellular models of PMDs while underscoring the significance of neuroinflammation as a potential driver in disease progression.
摘要：
■原发性线粒体疾病（PMD）是罕见的遗传性疾病，由对有效氧化磷酸化（OXPHOS）至关重要的基因突变引起，该基因突变可以影响线粒体功能。在这次审查中,我们检查了在原发性线粒体疾病（PMDs）的细胞模型中观察到的生物能量改变和氧化应激，揭示线粒体功能障碍和细胞病理学之间复杂的复杂性。我们探索了用于研究PMD的多种细胞模型，包括患者来源的成纤维细胞，诱导多能干细胞（iPSCs）和杂种。此外，我们还强调了氧化应激和神经炎症之间的联系。
■中枢神经系统（CNS）特别容易受到线粒体功能障碍的影响，因为它依赖于有氧代谢和OXPHOS的正确功能。与其他影响中枢神经系统的神经退行性疾病相似，患有PMD的个体除了神经变性外还表现出几种神经炎症特征，在线粒体疾病的小鼠模型中也广泛观察到这种模式。基于死后人脑组织的组织病理学分析和在PMD小鼠模型中的发现，我们认为，神经炎症不仅是神经变性的结果，而且是疾病进展的潜在致病机制，值得进一步研究。这种认识可能为目前缺乏有效治疗的这组破坏性疾病的新型治疗策略铺平道路。
结论：总之，这篇综述全面概述了PMD细胞模型中的生物能量改变和氧化还原失衡,同时强调了神经炎症作为疾病进展的潜在驱动因素的重要性.
■中枢神经系统（CNS）特别容易受到线粒体功能障碍的影响，因为它依赖于有氧代谢和OXPHOS的正确功能。与其他影响中枢神经系统的神经退行性疾病相似，患有PMD的个体除了神经变性外还表现出几种神经炎症特征，在线粒体疾病的小鼠模型中也广泛观察到这种模式。基于死后人脑组织的组织病理学分析和在PMD小鼠模型中的发现，我们认为，神经炎症不仅是神经变性的结果，而且是疾病进展的潜在致病机制，值得进一步研究。这种认识可能为目前缺乏有效治疗的这组破坏性疾病的新型治疗策略铺平道路。
结论：总之，这篇综述全面概述了PMD细胞模型中的生物能量改变和氧化还原失衡,同时强调了神经炎症作为疾病进展的潜在驱动因素的重要性.
