An effective method of treating various diseases associated with apoptosis
A new function of vitamin K, often known for its role in helping blood clot, has been discovered. Researchers at the Helmholtz Center in Munich, Germany, found that vitamin K in its reduced form acts as an antioxidant by effectively preventing cell death associated with ferroptosis.
Peroptosis refers to the natural form of apoptosis. In this process, intracellular iron plays a major role and is characterized by the oxidative degradation of cell membranes. The research team also identified FSP1 (ferroptosis suppressor protein-1) as a warfarin insensitivity enzyme that reduces vitamin K. This is an enzyme that scientists have only speculated about, but the identity of which has been unknown for more than half a century.
In recent years, feroptosis has been shown to be associated with many diseases, including Alzheimer’s disease and acute organ damage. The new findings support the view that vitamin K treatment could be a new and effective way to treat a variety of diseases associated with ferroptosis.
Vitamin K is a strong inhibitor of feroptosis.
Inhibition of peroptosis is considered a very promising approach to the treatment of many degenerative diseases. Therefore, new mechanisms and compounds that regulate ferroptosis are being studied extensively.
In this regard, the research team led by Dr. Eikan Mishima and Dr. Marcus Conrad from the Institute of Metabolism and Cell Death at the Helmholtz Center systematically studies naturally occurring vitamins and derivatives in collaboration with Tohoku University in Japan, the University of Wales. Ottawa in Canada, and Dresden University of Technology in Germany.
The first author, Dr. Eikan Mishima, “Surprisingly, we confirmed that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), can save cells and tissues from ferroptosis efficiently. “he explained.
Solving the mystery of vitamin K reductase FSP1
In 2019, the team of Dr. Marcus Conrad has already identified the FSP1 enzyme as an inhibitor of feroptosis. This time, we discovered that the fully reduced form of vitamin K (vitamin K hydroquinone) is a powerful lipophilic antioxidant that prevents ferroptosis by trapping free radicals in the lipid bilayer.
FSP1 was also found to be an enzyme that effectively converts vitamin K to vitamin K hydroquinone. Vitamin K is important for blood clotting. The researchers further determined that FSP1 is responsible for the vitamin K-reducing pathway that resists warfarin, one of the most commonly used anticoagulants.
Breakthrough in understanding vitamin K metabolism
By solving the identity of this enzyme, the team solved the final puzzle of vitamin K metabolism in blood coagulation and explained the molecular mechanisms why vitamin K is the antidote to warfarin overdose.
“Our findings bridge the two worlds of feroptosis research and vitamin K biology,” says Conrad.
As ferroptosis is likely to be one of the oldest forms of apoptosis, the team hypothesized that vitamin K may be one of the oldest forms of naturally occurring antioxidants. Therefore, it is expected that new aspects of the role of vitamin K in the evolution of life will be revealed.
The study was published in Nature. The original title is ‘A non-canonical vitamin K cycle is a potent inhibitor of ferroptosis’.
