Yokota Mutsumi
Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
Anat Sci Int. 2025 Mar;100(2):155-162. doi: 10.1007/s12565-024-00816-z. Epub 2024 Nov 29.
Changes in mitochondrial function and morphology contribute to the development of many neurological diseases. Parkinson's disease is one of the neurodegenerative diseases suspected to be associated with defects in mitochondrial function and quality control. The loss of dopaminergic neurons in the substantia nigra pars compacta is a well-known pathological feature of Parkinson's disease. It is important for elucidating the pathogenesis of Parkinson's disease to analyze mitochondrial function and morphology specific to dopaminergic neurons using live-cell imaging or electron microscopy. However, the cells differentiated into dopaminergic neurons from induced pluripotent stem cells generally comprise heterogeneous populations. We generated tyrosine hydroxylase (TH) reporter iPSC lines to distinguish dopaminergic neurons from other cells for live-cell imaging and electron microscopy. This review summarizes previous studies utilizing the TH reporter iPSC lines and discusses the importance of studying mitochondria specific to dopaminergic neurons. Additionally, it provides overviews of recent studies reporting changes in endoplasmic reticulum-mitochondrial contact sites in Parkinson's disease models.
线粒体功能和形态的改变促成了许多神经疾病的发展。帕金森病是一种疑似与线粒体功能和质量控制缺陷相关的神经退行性疾病。黑质致密部多巴胺能神经元的丧失是帕金森病一个众所周知的病理特征。利用活细胞成像或电子显微镜分析多巴胺能神经元特有的线粒体功能和形态，对于阐明帕金森病的发病机制很重要。然而，从诱导多能干细胞分化而来的多巴胺能神经元通常由异质群体组成。我们生成了酪氨酸羟化酶（TH）报告诱导多能干细胞系，以便在活细胞成像和电子显微镜检查中区分多巴胺能神经元和其他细胞。这篇综述总结了此前利用TH报告诱导多能干细胞系的研究，并讨论了研究多巴胺能神经元特有的线粒体的重要性。此外，它还概述了近期有关帕金森病模型中内质网-线粒体接触位点变化的研究报告。
