Study identifies MFF as key sensor and driver of ferroptotic cell death via mitochondria

Researchers show that mitochondrial fission factor (MFF) controls a chain of events during ferroptosis, linking mitochondrial dysfunction, peroxisomal and mitochondrial ROS production, and release of mitochondrial DNA into the cytosol through VDAC1 oligomerization. Using CRISPR knockouts, rescue experiments and pharmacological inhibitors in HeLa cells, they mapped how loss of MFF or its downstream partners (PEX5, MFN1/2, DRP1) alters cell survival after RSL3-induced ferroptotic stress.