德国慕尼黑亥姆兹中心Marcus Conrad、Eikan Mishima等研究人员合作发现,一个非经典的维生素K循环是一种有效的铁死亡抑制因子。这一研究成果于2022年8月3日在线发表在国际学术期刊《自然》上。
Author: 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, Mouro, Andr Santos Dias, Linkermann, Andreas, Geissler, Edward K., Nakagawa, Kiyotaka, Abe, Takaaki, Fedorova, Maria, Proneth, Bettina, Pratt, Derek A., Conrad, Marcus
Issue&Volume: 2022-08-03
Abstract: Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers2. 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 phylloquinone3—confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-44,5, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle6. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.
DOI: 10.1038/s41586-022-05022-3
Source: https://www.nature.com/articles/s41586-022-05022-3
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html