Mitochondrial dysfunction mediated by ER-calcium dysregulation in neurons derived from Alzheimer's disease patients.

ABSTRACT: Tight regulation of mitochondrial Ca²⁺ is essential for neuronal bioenergetics and cellular metabolism. Ca²⁺ transfer from ER-localized ryanodine receptors (RyR) and inositol triphosphate receptors (IP₃R) to the mitochondria maintains a steady Ca²⁺ source that fuels oxidative phosphorylation and ATP production. In Alzheimer's disease (AD), RyR-evoked Ca²⁺ release is markedly increased, contributing to synaptic deficits, protein mishandling, and memory impairment. Here, we demonstrate dysregulated RyR-Ca²⁺ release in neurons from familial and sporadic AD patients, and this directly compromises mitochondrial activity and contributes to AD cellular pathology. We measured an array of mitochondrial functions using fluorescent bio

SUBMITTER: Mustaly-Kalimi S 

PROVIDER: S-EPMC12305934 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature