Effective method for treating various diseases related to apoptosis
A new function of vitamin K, which helps blood clot, has been discovered. Researchers at the Helmholtz Center in Munich, Germany, found that vitamin K in its fully reduced form functions as an antioxidant by effectively inhibiting cell death associated with ferroptosis.
Peroptosis refers to the natural form of cell death. In this process, intracellular iron plays a major role and is characterized by oxidative degradation of cell membranes. In addition, the research team identified FSP1 (ferroptosis suppressor protein-1) as a warfarin (anticoagulant) insensitivity enzyme that reduces vitamin K. This is an enzyme that scientists have only speculated, but whose identity has not been known 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 may be a new and effective way to treat a variety of diseases related to ferroptosis.
Vitamin K is a potent inhibitor of feroptosis.
Cell death prevention is considered a very promising approach for the treatment of many degenerative diseases. Because of this, novel mechanisms and compounds regulating ferroptosis are being extensively studied.
The research team led by Dr. Eikan Mishima and Dr. Marcus Conrad of the Institute of Metabolism and Cell Death at the Helmholtz Center systematically studied naturally occurring vitamins and derivatives in collaboration with the University of Tohoku in Japan, the University of Ottawa in Canada, and the University of Technology Dresden in Germany.
“Surprisingly, we confirmed that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), can efficiently rescue cells and tissues from feroptosis,” said the first author, Dr. Eikan. explained.
Unraveling the secret of vitamin K reductase FSP1
In 2019, Dr. Conrad’s team had already identified the enzyme FSP1 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 inhibits ferroptosis by trapping free radicals in the lipid bilayer.
They also found that FSP1 is 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-reduction pathway that is resistant to warfarin, one of the most commonly used anticoagulants.
Breakthrough in understanding vitamin K metabolism
By unraveling the identity of this enzyme, the team solved the final puzzle of vitamin K metabolism in blood clotting and explained the molecular mechanisms why vitamin K constitutes the antidote to warfarin overdose.
“Our research bridges the two worlds of feroptosis research and vitamin K biology,” said Dr Conrad.
Since feroptosis is likely one of the oldest types of apoptosis, the team hypothesized that vitamin K might be one of the oldest types 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.
This study was published in Nature. The original title is ‘A non-canonical vitamin K cycle is a potent ferroptosis suppressor’.