Altered Mitochondrial Bioenergetics and Calcium Kinetics in Young-Onset PLA2G6 Parkinson's Disease iPSCs.

ABSTRACT: Parkinson's disease (PD) has emerged as a multisystem disorder affecting multiple cellular and organellar systems in addition to the dopaminergic neurons. Disease-specific induced pluripotent stem cells (iPSCs) model early developmental changes and cellular perturbations that are otherwise inaccessible from clinical settings. Here, we report the early changes in patient-derived iPSCs carrying a homozygous recessive mutation, R741Q, in the PLA2G6 gene. A gene-edited R747W iPSC line mirrored these phenotypes, thus validating our initial findings. Bioenergetic dysfunction and hyperpolarization of mitochondrial membrane potentials were hallmarks of the PD iPSCs. Further, a concomitant increase in glycolytic activity indicated a possible compensation for mitochondrial respiration. Elevated basa

SUBMITTER: Musthafa T 

PROVIDER: S-EPMC11973445 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature