Ferroptosis is a type of regulated cell death driven by iron-dependent oxidative damage to organelle and plasma membranes.  Ferroptosis has been implicated in heart disease, cancer, neurodegenerative disease, liver disease, and kidney failure. It was previously known that mitochondrial function is important for ferroptosis, but the underlying mechanisms were not understood.

In a study published online on August 13 in Molecular Cell, Albert Einstein College of Medicine scientists reported that optic atrophy 1 (OPA1)—an inner mitochondrial membrane protein that maintains mitochondrial structure and function—determines the sensitivity of human and mouse cells to ferroptosis. OPA1 promotes ferroptosis by increasing levels of unstable molecules (reactive oxygen species) within mitochondria and by suppressing the integrated stress response, a signaling pathway that helps mammalian cells cope with stressful conditions. The findings could aid in efforts to recruit ferroptosis in the killing of apoptosis-resistant cancer cells and, conversely, to limit ferroptosis in diseases where it is causing pathology.

The study’s corresponding author was Richard N. Kitsis, M.D., professor of medicine and of cell biology, the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease, and director of the Wilf Family Cardiovascular Research Institute at Einstein. Dr. Kitsis is also a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and of the Einstein-Mount Sinai Diabetes Research Center.