Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis.

ABSTRACT: Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of regulated cell death, that has been implicated in Alzheimer's disease and Parkinson's disease. Inhibition of cystine/glutamate antiporter could lead to mitochondrial fragmentation, mitochondrial calcium ([Ca²⁺]_m) overload, increased mitochondrial ROS production, disruption of the mitochondrial membrane potential (ΔΨ_m), and ferroptotic cell death. The observation that mitochondrial dysfunction is a characteristic of ferroptosis makes preservation of mitochondrial function a potential therapeutic option for diseases associated with ferroptotic cell death. Mitochondrial calcium levels are controlled via the mitochondrial calcium uniporter (MCU), the main entry point of Ca²⁺

SUBMITTER: Marmolejo-Garza A 

PROVIDER: S-EPMC10676387 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature