Analysis of dopaminergic neuron-specific mitochondrial morphology and function using tyrosine hydroxylase reporter iPSC lines

Abstract

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.