氧化还原酶POR和CYB5R1催化脂质过氧化以引发铁死亡。
The oxidoreductases POR and CYB5R1 catalyze lipid peroxidation to execute ferroptosis.
作者信息
Ai Youwei, Yan Bo, Wang Xiaodong
机构信息
National Institute of Biological Sciences, Beijing, China.
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
出版信息
Mol Cell Oncol. 2021 Feb 8;8(2):1881393. doi: 10.1080/23723556.2021.1881393. eCollection 2021.
Abstract
Our recent study showed that two oxidoreductases - NADPH-cytochrome P450 reductase (POR) and NADH-cytochrome b5 reductase (CYB5R1) - transfer electrons to oxygen to generate hydrogen peroxide (HO). HO then reacts with ferrous iron, generating hydroxyl radicals that cause peroxidation of polyunsaturated-fatty-acid chains of membrane phospholipids, resulting in plasma membrane rupture and ferroptosis.
摘要
我们最近的研究表明，两种氧化还原酶——NADPH-细胞色素P450还原酶（POR）和NADH-细胞色素b5还原酶（CYB5R1）——将电子传递给氧以生成过氧化氢（HO）。然后HO与亚铁反应，生成羟基自由基，这些自由基会导致膜磷脂的多不饱和脂肪酸链发生过氧化，从而导致质膜破裂和铁死亡。
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本文引用的文献
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Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1.铁死亡过程中细胞膜的损伤是由氧化还原酶 POR 和 CYB5R1 催化的磷脂氧化引起的。
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2
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3
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Nature. 2019 Nov;575(7784):688-692. doi: 10.1038/s41586-019-1705-2. Epub 2019 Oct 21.
4
FSP1 is a glutathione-independent ferroptosis suppressor.FSP1 是一种谷胱甘肽不依赖的铁死亡抑制因子。
Nature. 2019 Nov;575(7784):693-698. doi: 10.1038/s41586-019-1707-0. Epub 2019 Oct 21.
5
Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.炎性小体天冬氨酸特异性半胱氨酸蛋白酶 1（caspase-1）切割 GSDMD 决定细胞焦亡。
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6
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7
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8
Ferroptosis: an iron-dependent form of nonapoptotic cell death.铁死亡：一种依赖于铁的非细胞凋亡性细胞死亡形式。
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