Researchers at Helmholtz Munich have discovered a fresh use for vitamin K, which is often recognised for its role in blood clotting.
The scientists found that vitamin K in its fully reduced form functions as an antioxidant by effectively preventing ferroptotic cell death.
Cellular iron plays a significant role in the natural cell death process known as ferroptosis, which is also characterised by the oxidative breakdown of cellular membranes. Additionally, the scientists determined that FSP1 is the long-suspected but unidentified warfarin-insensitive enzyme lowering vitamin K.
In recent years, ferroptosis has been linked to a number of illnesses, including Alzheimer’s disease and acute organ damage. Thus, the current findings suggest that vitamin K therapy may be a fresh, effective method for treating these ferroptosis-related disorders.
The inhibition of ferroptosis is seen to be a very promising strategy for treating many degenerative diseases, hence research into new mechanisms and substances that control ferroptosis is ongoing.
Researchers from Tohoku University (Japan), University of Ottawa (Canada), and Technical University of Dresden (Germany), under the direction of Drs. Eikan Mishima and Marcus Conrad, both of the Institute of Metabolism and Cell Death at Helmholtz Munich, thoroughly examined a number of naturally occurring vitamins and their derivatives in order to identify these new molecules.
“Surprisingly, we identified that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), can efficiently rescue cells and tissues from undergoing ferroptosis” Dr. Eikan Mishima, first author of the study explained.
Ferroptosis suppressor protein-1, also known as FSP1, was discovered as a new and potent regulator of ferroptosis by a research team led by Dr. Marcus Conrad in 2019.
The study team has discovered that vitamin K hydroquinone, which has been totally reduced, functions as a potent lipophilic antioxidant and inhibits ferroptosis by capturing oxygen radicals in lipid bilayers. Furthermore, they discovered that FSP1 is the enzyme responsible for effectively reducing vitamin K to vitamin K hydroquinone, resulting in the activation of a brand-new, non-canonical vitamin K cycle.
The team went on to demonstrate that FSP1 is responsible for the vitamin K-reduction pathway being insensitive to warfarin, one of the most widely prescribed anticoagulants, given that vitamin K plays a crucial role in blood coagulation processes.
The last mystery surrounding vitamin K metabolism in blood clotting was resolved by identifying this enzyme, and this discovery also clarified the chemical basis for why vitamin K serves as the antidote for warfarin overdose. Therefore, the two fields of ferroptosis research and vitamin K biology are connected by the findings.
“They will serve as the stepping stone for the development of novel therapeutic strategies for diseases where ferroptosis has been implicated,” Dr. Marcus Conrad highlighted. “In addition, since ferroptosis most likely constitutes one of the oldest types of cell death, the researchers hypothesize that vitamin K might be one of the most ancient types of naturally occurring antioxidants. “Thus, new aspects of the role of vitamin K throughout the evolution of life are expected to be unveiled” Dr. Marcus Conrad explained.
Parvathy Sukumaran 
