Mitochondrial fission factor senses and governs ferroptosis.

Mitochondrial fission factor phosphorylation at Ser155 drives ferroptosis by promoting organelle fragmentation and oxidative stress in cells.

• Why it matters: Understanding how organelle dynamics influence ferroptosis is crucial for developing targeted therapies for diseases involving cell death, but the mechanisms linking these processes remain unclear.
• What they did: The study used quantitative phosphoproteomics to identify MFF as a ferroptosis regulator, developed a biosensor called MFF-SPARK to monitor phosphorylation in real time, and identified kinase-phosphatase pairs controlling this process.
• The result: Findings reveal that MFF phosphorylation accelerates ferroptosis through organelle remodeling, and pharmacological activation of this pathway with avermectin B1 enhances tumor sensitivity, offering new therapeutic strategies.