A mitochondrial inside-out iron-calcium signal reveals drug targets for Parkinson's disease.

ABSTRACT: Dysregulated iron or Ca²⁺ homeostasis has been reported in Parkinson's disease (PD) models. Here, we discover a connection between these two metals at the mitochondria. Elevation of iron levels causes inward mitochondrial Ca²⁺ overflow, through an interaction of Fe²⁺ with mitochondrial calcium uniporter (MCU). In PD neurons, iron accumulation-triggered Ca²⁺ influx across the mitochondrial surface leads to spatially confined Ca²⁺ elevation at the outer mitochondrial membrane, which is subsequently sensed by Miro1, a Ca²⁺-binding protein. A Miro1 blood test distinguishes PD patients from controls and responds to drug treatment. Miro1-based drug screens in PD cells discover Food and Drug Administration-approved T-type Ca²⁺

SUBMITTER: Bharat V 

PROVIDER: S-EPMC10804639 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature