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Fully reduced vitamin K found to effectively inhibit ferroptotic cell death

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A research team from Tohoku University reported on a novel function of vitamin K, commonly known for its importance in blood clotting. found to effectively inhibit thosis cell death. Ferroptosis is a natural form of cell death characterized by extensive lipid peroxidation in the cell membrane. In addition, the research team identified his FSP1 as a warfarin-insensitive vitamin K reductase. Ferroptosis has recently been implicated as a cause of acute organ damage in Alzheimer’s disease and many other diseases. This finding suggests that vitamin K treatment may be a new and powerful strategy to ameliorate these ferroptosis-related diseases.

Vitamin K is a powerful ferroptosis inhibitor

Prevention of ferroptosis is considered to be a highly promising approach for the treatment of many degenerative diseases, and therefore new mechanisms and compounds that regulate ferroptosis are being extensively investigated. To identify these new molecules, a research team led by Dr. Eikan Mishima (Tohoku University) and Dr. Marcus Konrad (Helmholtz Munich) systematically studied several natural vitamins and their derivatives. “Surprisingly, we found that vitamin K, such as phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), can effectively rescue cells and tissues from ferroptosis,” explained Dr. Mishima. did.

Elucidation of the long-awaited vitamin K reductase FSP1

In 2019, a team of researchers led by Dr. Conrad identified an enzyme that is a novel and potent inhibitor of ferroptosis: ferroptosis-inhibitory protein-1, short FSP1. (ie, vitamin K hydroquinone) acts as a potent lipophilic antioxidant and prevents ferroptosis by trapping oxygen radicals in the lipid bilayer. Furthermore, they identified FSP1 as an enzyme that efficiently reduces vitamin K to vitamin K hydroquinone, thereby driving a new non-canonical vitamin K cycle. Since vitamin K plays an important role in the blood clotting process, the team further implicates his FSP1 in the vitamin K reduction pathway, which is unresponsive to warfarin, one of the most prescribed anticoagulants. showed.

Breakthrough in understanding vitamin K metabolism

Elucidating the identity of this enzyme has solved the final mystery of vitamin K metabolism in blood clotting and revealed the molecular mechanism why vitamin K is an antidote to warfarin overdose. “Our results have the potential to bridge the two worlds of ferroptosis research and vitamin K biology,” said Dr. Mishima and Dr. Conrad. It will be a stepping stone for developing therapeutic strategies.” Furthermore, since ferroptosis most likely constitutes one of the oldest types of cell death, researchers hypothesize that vitamin K may be one of the most primitive types of cell death. . naturally derived antioxidants“Thus, it is hoped that new aspects of the role of vitamin K in the evolution of life will be revealed.”

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