迄今为止，真核生物中还没有真正的铁排泄生理机制，也没有可以控制吸收、储存和排泄这三个基本生物过程的生理“执行器”。在这里，我们观察到杜邦嗜热丝孢菌在冷胁迫下积累蒽醌可以实现这一过程。通过突变分析，我们发现蒽醌缺乏的突变体ΔAn由于采取了一种罕见的生活方式，没有内吞作用，但膜源性囊泡积累，从而积累了亚铁和总游离铁。蒽醌补体表明 ΔAn 中的囊泡可以包裹外源蒽醌诱导的颗粒，以防止与真菌内部接触。对 ΔAn 的详细化学研究导致了一种在空气中不稳定的稀有无氧麦角甾烯的表征，作为 ΔAn 中的主要膜类固醇，表明 ΔAn 细胞内部缺氧，与 ΔAn 中极低的耗氧率一致。一系列的生理和代谢分析表明，蒽醌参与亚铁的输出和促进含氧代谢物的形成，包括用于内吞作用的麦角甾醇和用于铁储存的铁螯合剂。此外，我们发现具有众所周知的心脏毒性副作用的抗癌剂米托蒽醌和丹参中用于治疗心血管疾病的主要萜类衍生多环芳香族化合物在人类癌细胞中均表现出强大的亚铁转运能力。我们的研究结果为多环芳烃在自然和药理学中的潜在机制提供了新的见解，并为开发用于膜运输、铁稳态和抗冷的潜在疗法和药物提供了新策略。© 2024 作者。约翰·威利 (John Wiley) 出版的《微生物生物技术》

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 ΔAn 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 ΔAn could coat the extrinsic anthraquinone-induced granules to prevent contact with the fungal interiors. Detailed chemical investigation on ΔAn led to characterization of a rare oxygen-free ergosterene with unstable nature in air as the major membrane steroid in ΔAn, suggesting hypoxia inner in ΔAn cells, consistent with dramatically low oxygen-consuming rates in ΔAn. 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.© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.