Ferroptotic pores induce Ca²⁺ fluxes and ESCRT-III activation to modulate cell death kinetics.

ABSTRACT: Ferroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca²⁺ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of a few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca²⁺ fluxes during ferroptosis induce the activation of the ESCRT-III-dependent membrane repair machinery, which counterbalances the ki

SUBMITTER: Pedrera L 

PROVIDER: S-EPMC8167089 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature