2. Academic Validation
  3. Melanin precursors mediated adaption to temperature changes in fungus and animal via inhibition of lipid-mediated ferroptosis

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

  • Sci China Life Sci. 2023 Mar 17. doi: 10.1007/s11427-022-2265-6.
Xiaoyu Yang # 1,  Yonghong Chen # 1,  Longlong Zhang # 1,  Jiangbo He # 2,  Qunfu Wu 1,  Shuhong Li 1,  Donglou Wang 1,  Jianghui Gou 1,  Zhuang Wu 1,  Keqin Zhang 1,  Shenghong Li 3,  Xuemei Niu 4
Affiliations

Affiliations

  • 1 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming, 650032, China.
  • 2 Kunming Key Laboratory of Respiratory Disease, Kunming University, Kunming, 650214, China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. shli@mail.kib.ac.cn.
  • 4 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming, 650032, China. xmniu@ynu.edu.cn.
  • # Contributed equally.
PMID: 36949229 DOI: 10.1007/s11427-022-2265-6
Abstract

The discovery of biological activities of Natural Products plays a vital part in drug development. The 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 mass. Deficiency in 1 caused melanin loss and accumulated extra lipid mass, unexpectedly leading to seriously damaged mitochondria diagnostic for Ferroptosis. Further 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 peroxidation. We also found that melanin in mice lowered lipid level but enhanced animal resistance to cold stress. Treatment with melanin precursors significantly increased mouse cell survival rate under cold stress. Our 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 stress. These findings opened a perspective for developing anti-cold and anti-ferroptosis therapeutics and agents.

Keywords

anti-cold; ferroptosis; lipid; melanin; precursor; temperature change.

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