Related Experiment Video

Updated: Apr 22, 2026

Genome-wide Analysis of Histone Modifications Distribution using the Chromatin Immunoprecipitation Sequencing Method in Magnaporthe oryzae
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Genome-wide Analysis of Histone Modifications Distribution using the Chromatin Immunoprecipitation Sequencing Method in Magnaporthe oryzae

Published on: June 2, 2021

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MoCox6 is a regulator of mitophagy and a druggable target in Magnaporthe oryzae

Ming-Hua Wu1,2,3,4, Ya-Nan Lv1, Hui Li5

  • 1State Key Laboratory for Quality and Safety of Agro-Products, Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Nature Microbiology
|April 20, 2026
PubMed

Insights

Researchers discovered MoCox6, an inner mitochondrial membrane protein, regulates mitophagy in the fungus Magnaporthe oryzae. Inhibiting this process with Pan-RAS-IN-1 shows broad-spectrum antifungal activity and suppresses rice blast disease.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Mycology

Background:

  • Mitophagy maintains cellular health by removing damaged mitochondria and is a potential antifungal target.
  • Knowledge of inner mitochondrial membrane (IMM) regulators of mitophagy is limited.

Purpose of the Study:

  • To identify novel IMM regulators of mitophagy in Magnaporthe oryzae.
  • To investigate the role of MoCox6 in mitophagy and its potential as an antifungal target.

Main Methods:

  • Identified MoCox6 as an IMM regulator binding MoAtg5 and MoAtg14.
  • Investigated MoSirt5's role in desuccinylating MoCox6.
  • Performed structural analysis of the MoSirt5-MoCox6 interface.
  • Screened for small-molecule inhibitors of MoCox6.
  • Assessed the impact of COX6 deletion on fungal growth and virulence.
  • Evaluated the antifungal activity of Pan-RAS-IN-1 in vitro and in planta.

Main Results:

  • MoCox6 was identified as an IMM regulator mediating mitophagy by binding MoAtg5 and MoAtg14 after outer mitochondrial membrane rupture.
  • MoSirt5 regulates MoCox6 activity via desuccinylation at K144.
  • Structural analysis revealed MoCox6 residue D95 is crucial for both mitophagy and metabolic competence.
  • Deletion of the COX6 gene impaired vegetative growth and virulence in M. oryzae and Alternaria alternata.
  • High-throughput screening identified Pan-RAS-IN-1, a small molecule that inhibits MoCox6 and mitophagy, suppressing M. oryzae virulence.
  • Pan-RAS-IN-1 demonstrated broad-spectrum antifungal activity and significantly reduced rice blast incidence when applied to rice plants.

Conclusions:

  • MoCox6 is a key IMM regulator of mitophagy in M. oryzae, essential for fungal growth and virulence.
  • Targeting MoCox6 with inhibitors like Pan-RAS-IN-1 offers a promising strategy for controlling fungal pathogens, including rice blast disease.

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