Vitamin K Found To Prevent Cell Death

A group of scientists from Helmholtz Munich has identified a new use for vitamin K, typically recognized for its part in blood clotting. In its fully reduced configuration, the researchers discovered that vitamin K operates as an anti-oxidant by efficiently inhibiting ferroptotic cell death. Ferroptosis is a natural kind of cell death in which cellular iron plays a significant part and is identified by the oxidative breakdown of cellular membranes. Additionally, the scientists identified FSP1 as the warfarin-insensitive enzyme reducing vitamin K, the identity of which had been hypothesized yet stayed unidentified for at least a half-century.

In the last few years, ferroptosis has been connected to various health problems, including Alzheimer’s disease and acute organ damage. This report suggests that vitamin K therapy could be a new, effective method to address different conditions associated with ferroptosis.

An effective ferroptosis suppressor

Since ferroptosis prevention is seen as an exceptionally promising method for treating several degenerative diseases. New systems and compounds controlling ferroptosis are thoroughly being looked into. 

To determine these new molecules, a group of scientists led by Dr. Eikan Mishima and Dr. Marcus Conrad, both from the Institute of Metabolism and Cell Death at Helmholtz Munich, alongside partners from Tohoku University (Japan), University of Ottawa (Canada), and Technical University of Dresden (Germany), methodically analyzed several naturally occurring vitamins, along with 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, detailed.

Discovering a powerful anti-oxidant

In 2019 a group of scientists around Dr. Marcus Conrad identified an enzyme as a unique and solid inhibitor of ferroptosis: ferroptosis suppressor protein-1 (FSP1). Scientists have learned that the fully reduced form of vitamin K (vitamin K hydroquinone) is a powerful lipophilic anti-oxidant that restrains ferroptosis by capturing oxygen radicals in lipid bilayers.

Additionally, they found that FSP1 is the enzyme that successfully transforms vitamin K into vitamin K hydroquinone, leading to a new non-canonical vitamin K cycle. Since vitamin K is essential in blood clotting, the researchers also established that FSP1 is responsible for a vitamin K-reduction pathway that is resistant to warfarin, amongst the most frequently used anticoagulants.

A Breakthrough in understanding vitamin K

Unraveling the identity of this enzyme was the last piece of the puzzle for vitamin K metabolism in blood clotting. It clarified the molecular mechanism of why vitamin K makes up the remedy for overdosing on 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 emphasizes.

Additionally, since ferroptosis most likely comprises one of the oldest forms of cell death, scientists hypothesize that vitamin K could be among the most ancient types of naturally occurring anti-oxidants. “Thus, new aspects of the role of vitamin K throughout the evolution of life are expected to be unveiled,” Dr. Marcus Conrad detailed.

Originally published by: ScitechDaily

Reference: “A non-canonical vitamin K cycle is a potent ferroptosis suppressor” by Eikan Mishima, Junya Ito, Zijun Wu, Toshitaka Nakamura, Adam Wahida, Sebastian Doll, Wulf Tonnus, Palina Nepachalovich, Elke Eggenhofer, Maceler Aldrovandi, Bernhard Henkelmann, Ken-ichi Yamada, Jonas Wanninger, Omkar Zilka, Emiko Sato, Regina Feederle, Daniela Hass, Adriano Maida, André Santos Dias Mourão, Andreas Linkermann, Edward K. Geissler, Kiyotaka Nakagawa, Takaaki Abe, Maria Fedorova, Bettina Proneth, Derek A. Pratt, and Marcus Conrad, 3 August 2022, Nature.
DOI: 10.1038/s41586-022-05022-3