Nature: A non-canonical vitamin K cycle prevents ferroptosis
In our most recent collaborative study with several partners from the SPP 2306 (Conrad, Fedorova, Linkermann), we report that vitamin K is a potent suppressor of ferroptosis by preventing oxidative damage to cellular membranes. So far, vitamin K has been well-known for its role in blood clotting and bone calcification, and its discovery dating almost 100 year ago was awarded with the Nobel Prize in Physiology or Medicine to Henrik Carl Peter Dam and Edward Adelbert Doisy in 1943. Mechanistically, we demonstrate that ferroptosis suppressor protein-1 (FSP1) reduces oxidized vitamin K to its hydroquinone form, thus driving a novel non-canonical vitamin K cycle that potently suppresses ferroptosis in cells and mice. We further show that FSP1 is the long sought-after warfarin-resistant vitamin K reductase, thus solving one of the last riddles in vitamin K biology. Findings presented in our present work will therefore have immediate implications for both vitamin K and ferroptosis research (Figure adopted from Mishima et al., Nature 2022).