Researchers describe a new function of vitamin K, which is well recognised for its role in blood clotting. The researchers observed that the completely reduced version of vitamin K effectively inhibits ferroptosis cell death.
Ferroptosis has been linked to Alzheimer’s disease, acute organ damage, and a variety of other disorders in recent years. Thus, the current data suggest that vitamin K therapy might be a new and potent method for treating ferroptosis-related disorders.
Vitamin K is a potent ferroptosis suppressor
Since ferroptosis prevention is considered a highly promising approach for the therapy of many degenerative diseases, new mechanisms and compounds regulating ferroptosis are extensively being explored. To identify these new molecules, a team of researchers led by Dr. Eikan Mishima and Dr. Marcus Conrad, both from the Institute of Metabolism and Cell Death at Helmholtz Munich, along with collaborators from Tohoku University (Japan), University of Ottawa (Canada) and Technical University of Dresden (Germany), systematically studied a number of naturally occurring vitamins, as well as their derivatives. “Surprisingly, we identified that vitamin K, including phylloquinone (vitamin K1) and menaquinone-4 (vitamin K2), is able to efficiently rescue cells and tissues from undergoing ferroptosis” Dr. Eikan Mishima, first author of the study explained.
Unraveling the long sought-after vitamin K reducing enzyme FSP1
In 2019, a team of researchers led by Dr. Marcus Conrad found ferroptosis suppressor protein-1, or FSP1, as a unique and potent regulator of ferroptosis. The researchers discovered that the completely reduced form of vitamin K (vitamin K hydroquinone) is a potent lipophilic antioxidant that suppresses ferroptosis by trapping oxygen radicals in lipid bilayers. Furthermore, they discovered that FSP1 is the enzyme that effectively converts vitamin K to vitamin K hydroquinone, resulting in a unique non-canonical vitamin K cycle. Because vitamin K is essential for blood clotting, the researchers discovered that FSP1 is responsible for a vitamin K-reduction pathway that is resistant to warfarin, one of the most routinely used anticoagulants.
Breakthrough in understanding vitamin K metabolism
Unraveling the identity of this enzyme solved the last riddle of vitamin K metabolism in blood clotting and elucidated the molecular mechanism of why vitamin K constitutes the antidote for overdosing of warfarin. “Our results therefore link the two worlds of ferroptosis research and vitamin K biology. 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.