线粒体是真核细胞中细胞代谢和生理活动的关键细胞器。人类线粒体拥有自身的遗传物质(mtDNA)，这是由母系遗传的37个基因，编码13个氧化磷酸化反应的多肽，以及22个tRNA和2个rRNA用于翻译。mtDNA突变与多种退行性和神经肌肉疾病相关。然而，线粒体疾病的病理生理学，尤其是阈值效应和组织特异性，尚不清楚，并且目前没有有效的治疗方法。尤其是，缺乏合适的细胞和动物疾病模型一直是深入揭示母系遗传疾病的病理生理学和开发有效疗法的重要障碍。使用从患者中获得的人类诱导多能干细胞（iPSCs）衍生的特定细胞系，例如内耳毛细胞，是深入理解线粒体疾病致病机制和开发治疗干预措施的一种革命性方法。在本研究中，我们回顾了近年来患者衍生iPSCs作为线粒体疾病离体模型的最新进展。这些患者衍生的iPSCs已经分化为具有特定靶向细胞（例如视网膜神经节细胞）和最终器官样结构的细胞，用于疾病建模。这些疾病模型推动了我们对于母系遗传疾病病理生理学的理解，并为这些疾病的治疗干预措施迈出了一步。©2023. 中华民国（台湾）国家科学委员会。

Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 polypeptides for oxidative phosphorylation, and 22 tRNAs and 2 rRNAs for translation. mtDNA mutations are associated with a wide spectrum of degenerative and neuromuscular diseases. However, the pathophysiology of mitochondrial diseases, especially for threshold effect and tissue specificity, is not well understood and there is no effective treatment for these disorders. Especially, the lack of appropriate cell and animal disease models has been significant obstacles for deep elucidating the pathophysiology of maternally transmitted diseases and developing the effective therapy approach. The use of human induced pluripotent stem cells (iPSCs) derived from patients to obtain terminally differentiated specific lineages such as inner ear hair cells is a revolutionary approach to deeply understand pathogenic mechanisms and develop the therapeutic interventions of mitochondrial disorders. Here, we review the recent advances in patients-derived iPSCs as ex vivo models for mitochondrial diseases. Those patients-derived iPSCs have been differentiated into specific targeting cells such as retinal ganglion cells and eventually organoid for the disease modeling. These disease models have advanced our understanding of the pathophysiology of maternally inherited diseases and stepped toward therapeutic interventions for these diseases.© 2023. National Science Council of the Republic of China (Taiwan).