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外源性铁诱导 中的孢子依赖 NADPH 氧化酶的铁死亡

Exogenous Iron Induces NADPH Oxidases-Dependent Ferroptosis in the Conidia of .

机构信息

School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.

Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, Connecticut 06269, United States.

出版信息

J Agric Food Chem. 2021 Nov 17;69(45):13608-13617. doi: 10.1021/acs.jafc.1c04411. Epub 2021 Nov 8.

DOI:10.1021/acs.jafc.1c04411
PMID:34747604
Abstract

is saprophytic soil fungus that contaminates seed crops with the carcinogenic secondary metabolite aflatoxin, posing a significant threat to humans and animals. Ferrous sulfate is a common iron supplement that is used to the treatment of iron-deficiency anemia. Here, we identified an unexpected inhibitory role of ferrous sulfate on . With specific fluorescent dyes, we detected several conidial ferroptosis hallmarks in conidia under the treatment of 1 mM Fe, including nonapoptosis necrosis, iron-dependent, lipid peroxide accumulation, and ROS burst. However, unlike traditional ferroptosis in mammals, Fe triggered conidial ferroptosis in was regulated by NADPH oxidase (NOXs) activation instead of Fenton reaction. Transcriptomic and some other bioinformatics analyses showed that NoxA in might be a potential target of Fe, and thus led to the occurrence of conidial ferroptosis. Furthermore, deletion mutant was constructed, and both ROS generation and conidial ferroptosis in was reduced when exposed to Fe. Taken together, our study revealed an exogenous Fe-triggered conidial ferroptosis pathway mediated by NoxA of , which greatly contributes to the development of an alternative strategy to control this pathogen.

摘要

黄曲霉是一种腐生土壤真菌,它会污染种子作物,使其产生致癌的次级代谢物黄曲霉毒素,对人类和动物构成重大威胁。硫酸亚铁是一种常用的铁补充剂,用于治疗缺铁性贫血。在这里,我们发现硫酸亚铁对具有意想不到的抑制作用。使用特定的荧光染料,我们在 1mMFe 的处理下,在分生孢子中检测到几种分生孢子铁死亡的特征,包括非凋亡坏死、铁依赖性、脂质过氧化物积累和 ROS 爆发。然而,与哺乳动物中的传统铁死亡不同,Fe 触发的是由 NADPH 氧化酶(NOXs)激活而不是 Fenton 反应调节的分生孢子铁死亡。转录组和其他一些生物信息学分析表明,中的 NoxA 可能是 Fe 的潜在靶标,从而导致分生孢子铁死亡的发生。此外,还构建了缺失突变体,当暴露于 Fe 时,中 ROS 的产生和分生孢子铁死亡减少。总之,我们的研究揭示了一种由中的 NoxA 介导的外源 Fe 触发的分生孢子铁死亡途径,这为开发控制这种病原体的替代策略做出了巨大贡献。

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