Reduced ER-mitochondrial contact sites and mitochondrial Ca²⁺ flux in PRKN-mutant patient tyrosine hydroxylase reporter iPSC lines.

ABSTRACT: Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in mitochondrial dynamics, calcium signaling, and autophagy. Disruption of the ERMCS has been linked to several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We previously established tyrosine hydroxylase reporter (TH-GFP) iPSC lines from a PD patient with a PRKN mutation to perform correlative light-electron microscopy (CLEM) analysis and live cell imaging in GFP-expressing dopaminergic neurons. Here, we analyzed ERMCS in GFP-expressing PRKN-mutant dopaminergic neurons from patients using CLEM and a proximity ligation assay (PLA). T

SUBMITTER: Yokota M 

PROVIDER: S-EPMC10514478 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature