2. Academic Validation
  3. Exosomes drive ferroptosis by stimulating iron accumulation to inhibit bacterial infection in crustaceans

Exosomes drive ferroptosis by stimulating iron accumulation to inhibit bacterial infection in crustaceans

  • J Biol Chem. 2023 Nov 15:105463. doi: 10.1016/j.jbc.2023.105463.
Qian Sun 1,  Jiawen Yang 1,  Ming Zhang 1,  Yongsheng Zhang 1,  Hongyu Ma 1,  Ngoc Tuan Tran 1,  Xiuli Chen 2,  Yueling Zhang 1,  Kok-Gan Chan 3,  Shengkang Li 4
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou 515063, China; Institute of Marine Sciences, Shantou University, Shantou 515063, China; STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou 515063, China.
  • 2 Guangxi Academy of Fishery Sciences, Guangxi Key Laboratory of Aquatic Genetic Breeding and Healthy Aquaculture, Guangxi Nanning 530021, China.
  • 3 Institute of Marine Sciences, Shantou University, Shantou 515063, China; Division of Genetics and Molecular Biology, Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  • 4 Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou 515063, China; Institute of Marine Sciences, Shantou University, Shantou 515063, China; STU-UMT Joint Shellfish Research Laboratory, Shantou University, Shantou 515063, China. Electronic address: lisk@stu.edu.cn.
PMID: 37977221 DOI: 10.1016/j.jbc.2023.105463
Abstract

Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of Ferroptosis and the inhibition of Bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that Cytochrome P450 (CYP) can effectively trigger Ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 (STEAP4) in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that STEAP4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE), which activates the Peroxisome Proliferator-activated Receptor (PPAR). Consequently, the downstream target of PPAR, cluster of differentiation 36 (CD36), promotes intracellular fatty acid accumulation, lipid peroxidation, and Ferroptosis. These significant findings shed LIGHT on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating Bacterial infections in this species.

Keywords

CD36; CYP; PPAR; STEAP4; crustaceans; exosomes; ferroptosis.

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