H2S-mediated protein S-sulfhydration modulates infectivity and autophagy in the rice blast fungus

Hong Hu, Mengyuan Qin, Jiening Zhang, Jintao Jiang, Zhiqin Su, Lun Guan, Zhiguang Qu, Caiyun Liu, Xuan Cai, Zhiyong Ren, Yuhang Duan, Deyao Zhang, Hao Liu, Lu Zheng, Junbin Huang and Xiao-Lin Chen ()
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Hong Hu: Huazhong Agricultural University
Mengyuan Qin: Huazhong Agricultural University
Jiening Zhang: Huazhong Agricultural University
Jintao Jiang: Huazhong Agricultural University
Zhiqin Su: Huazhong Agricultural University
Lun Guan: Huazhong Agricultural University
Zhiguang Qu: Huazhong Agricultural University
Caiyun Liu: Huazhong Agricultural University
Xuan Cai: Huazhong Agricultural University
Zhiyong Ren: Huazhong Agricultural University
Yuhang Duan: Huazhong Agricultural University
Deyao Zhang: Huazhong Agricultural University
Hao Liu: Huazhong Agricultural University
Lu Zheng: Huazhong Agricultural University
Junbin Huang: Huazhong Agricultural University
Xiao-Lin Chen: Huazhong Agricultural University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Hydrogen sulfide (H2S) regulates cellular activities in plants and mammals through S-sulfhydration, a post-translational modification of proteins. The role of H2S and its molecular targets in fungi, however, remains unclear. Here we show that H2S, synthesized by cystathionine γ-lyase (CSE1) in the rice blast fungus Magnaporthe oryzae, is essential for optimal fungal infection. Excessive H2S, through S-sulfhydration, impairs fungal infectivity by inhibiting autophagy. Using quantitative proteomics, we identify numerous S-sulfhydrated proteins in M. oryzae, including the autophagy-related protein ATG18. S-sulfhydration of a cysteine residue (Cys78) in ATG18 is essential for its binding to phosphatidylinositol 3-phosphate, thereby maintaining the protein’s structural stability and regulating autophagy. Thus, our study reveals a mechanism by which H2S-mediated S-sulfhydration controls autophagy in the rice blast fungus and suggests the potential use of H2S donors as a strategy to control fungal diseases by targeting fungal development and infection structures.

Date: 2025
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DOI: 10.1038/s41467-025-61582-8

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