A non-canonical vitamin K cycle is a potent ferroptosis suppressor

Mishima, Eikan; Ito, Junya; Wu, Zijun; Nakamura, Toshitaka; Wahida, Adam; Doll, Sebastian; Tonnus, Wulf; Nepachalovich, Palina; Eggenhofer, Elke; Aldrovandi, Maceler; Henkelmann, Bernhard; Yamada, Ken‐ichi; Wanninger, Jonas; Zilka, Omkar; Sato, Emiko; Feederle, Regina; Hass, Daniela; Maida, Adriano; Mourão, André; Linkermann, Andreas; Geissler, Edward K.; Nakagawa, Kiyotaka; Abe, Takaaki; Fedorova, Maria; Proneth, Bettina; Pratt, Derek A.; Conrad, Marcus

doi:10.1038/s41586-022-05022-3

articleNatureAug 3, 2022HYBRID OA

A non-canonical vitamin K cycle is a potent ferroptosis suppressor

EMEikan Mishima JIJunya Ito ZWZijun Wu TNToshitaka Nakamura AWAdam Wahida

Tohoku University · Helmholtz Zentrum München · +8 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Abstract Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation 1 , has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers 2 . Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K—a group of naphthoquinones that includes menaquinone and phylloquinone 3 —confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl…

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Topics & keywords

Topics

Keywords

Lipid peroxidation
Vitamin E
GPX4
Programmed cell death
Reductase
Chemistry
Vitamin K epoxide reductase
Apoptosis

UN Sustainable Development Goals

Good health and well-being

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