Melanin precursors mediated adaption to temperature changes in fungus and animal via inhibition of lipid-mediated ferroptosis

作     者：Xiaoyu Yang Yonghong Chen Longlong Zhang Jiangbo He Qunfu Wu Shuhong Li Donglou Wang Jianghui Gou Zhuang Wu Keqin Zhang Shenghong Li Xuemei Niu 

作者机构：State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnanand Key Laboratory for Southwest Microbial Diversity of the Ministry of EducationYunnan UniversityKunming 650032China State Key Laboratory of Phytochemistry and Plant Resources in West ChinaKunming Institute of BotanyChinese Academy of SciencesKunming 650201China Kunming Key Laboratory of Respiratory DiseaseKunming UniversityKunming 650214China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2023年第66卷第8期

页      面：1800-1817页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(21977086,82260691,and 21867018) “Double tops”from Yunnan Province and Yunnan University(202201BF070001-012) the Yunnan Innovative Research Team for Discovery and Biosynthesis of Bioactive Natural Products(2018HC012) 

主　　题：melanin precursor lipid ferroptosis temperature change anti-cold 

摘      要：The discovery of biological activities of natural products plays a vital part in drug *** mechanism by which organisms respond to temperature changes via biosynthesis of natural products remained largely cryptic.A thermophilic fungus under cold stress turned black and accumulated a polyketide metabolite 1 and lipid *** in 1 caused melanin loss and accumulated extra lipid mass,unexpectedly leading to seriously damaged mitochondria diagnostic for *** analysis revealed that lipid mass induced by cold stress intensively increased ferroptosis risk and 1 functioned as cell wall reinforcer against mass lipid accumulation and as reactive oxygen species scavenger against lipid *** also found that melanin in mice lowered lipid level but enhanced animal resistance to cold *** with melanin precursors significantly increased mouse cell survival rate under cold *** results unveiled a metabolite-lipid-ferroptosis-cold relationship,which provided mechanistic insights into the functions of most common metabolites and into diseases related to cold *** findings opened a perspective for developing anti-cold and anti-ferroptosis therapeutics and agents.