Thermophilic fungus uses anthraquinones to modulate ferrous excretion, sterol-mediated endocytosis, and iron storage in response to cold stress

doi:10.1111/1751-7915.70002

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	Thermophilic fungus uses anthraquinones to modulate ferrous excretion, sterol-mediated endocytosis, and iron storage in response to cold stress
	Li, Shuhong; Wang, Donglou; He, Jiangbo; Liao, Chunhua; Zuo, Zhangxin; Li, Shenghong; Niu, Xuemei
	2024
发表期刊	MICROBIAL BIOTECHNOLOGY
ISSN	1751-7915
卷号	17 期号:9 页码:e70002
摘要	To date, there are no real physiological mechanisms for iron excretion in eukaryote, and no physiological actuator that can control all the three fundamental biologic processes of absorption, storage, and excretion. Here, we observed that the accumulation of anthraquinones by Thermomyces dupontii under cold stress can achieve this process. Through mutation analysis, we found that mutant Delta An deficiency in anthraquinones accumulated ferrous and total free iron due to adopting a rare lifestyle with no endocytosis but accumulation of membrane-derived vesicles. Anthraquinone complement indicated that the vesicles in Delta An could coat the extrinsic anthraquinone-induced granules to prevent contact with the fungal interiors. Detailed chemical investigation on Delta An led to characterization of a rare oxygen-free ergosterene with unstable nature in air as the major membrane steroid in Delta An, suggesting hypoxia inner in Delta An cells, consistent with dramatically low oxygen-consuming rates in Delta An. A series of physiological and metabolic analyses indicated anthraquinones were involved in exporting ferrous and promoting formation of oxygen-containing metabolites, including ergosterols for endocytosis and iron chelators for iron storage. Moreover, we found that both the anticancer agent mitoxantrone with well-known-cardiotoxicity side effect and the major terpenoid-derived polycyclic aromatics from Danshen for treating cardiovascular disease showed potent ferrous transporting capabilities in human cancer cells. Our findings provide a novel insight into the underlying mechanisms of polycyclic aromatics in nature and pharmacology, and offer a new strategy for developing potential therapeutics and agents for membrane transport, iron homestasis, and anticold.Up to now, regulation of iron homeostasis by metabolites has rarely been characterized. Moreover, no excretory mechanisms for iron in fungi have been reported. In this study, we found that Thermomyces dupontii can accumulate a large amount of anthraquinones under cold stress. The anthraquinones can release free ferric ions, reduce ferric to ferrous ions, and export ferrous ions, greatly enhancing thermophilic fungus to survive in the bio-system environment. Furthermore, a lack of the anthraquinones can inhibit oxygen-dependent ergosterol-mediated endocytosis, leading to an self-imposed isolation via oxygen-free ergosterene-mediated cell membranes. Importantly, the well-known anthraquinone compound Mitoxantraquinone for anticancer and the main terpenoid polycyclic aromatic metabolites in traditional Chinese medicine Danshen for the treatment of cardiovascular diseases both exhibit strong ferrous ions transport capabilities. Our findings provided new insights for developing potential therapies and drugs for iron homeostasis and drug delivery.image
DOI	10.1111/1751-7915.70002
WOS记录号	WOS:001303086400001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75935
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Li, Shuhong,Wang, Donglou,He, Jiangbo,et al. Thermophilic fungus uses anthraquinones to modulate ferrous excretion, sterol-mediated endocytosis, and iron storage in response to cold stress[J]. MICROBIAL BIOTECHNOLOGY,2024,17(9):e70002.
APA	Li, Shuhong.,Wang, Donglou.,He, Jiangbo.,Liao, Chunhua.,Zuo, Zhangxin.,...&Niu, Xuemei.(2024).Thermophilic fungus uses anthraquinones to modulate ferrous excretion, sterol-mediated endocytosis, and iron storage in response to cold stress.MICROBIAL BIOTECHNOLOGY,17(9),e70002.
MLA	Li, Shuhong,et al."Thermophilic fungus uses anthraquinones to modulate ferrous excretion, sterol-mediated endocytosis, and iron storage in response to cold stress".MICROBIAL BIOTECHNOLOGY 17.9(2024):e70002.

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