Bacterial CipB is an exogenous receptor to drive the mitophagy-TFEB axis and promote pathogenesis

Shuai Liu1,2, Lina Ma1, Ruiqi Lv1

  • 1State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University , Wuhan, China.

The Journal of Cell Biology
|November 21, 2025
PubMed

Insights

This study identifies CipB, a bacterial protein, as a novel mitophagy receptor that helps pathogens evade immune responses. CipB manipulates host mitophagy to promote bacterial survival and virulence.

Area of Science:

  • Cell Biology
  • Microbiology
  • Immunology

Background:

  • Mitophagy is crucial for cellular homeostasis, regulating energy, inflammation, and immunity by degrading mitochondria.
  • Pathogens often evolve mechanisms to subvert host cellular processes for their own benefit.

Purpose of the Study:

  • To identify novel exogenous mitophagy receptors used by bacterial pathogens.
  • To elucidate the mechanism by which bacterial effectors manipulate host mitophagy for pathogenesis.

Main Methods:

  • Identification of CipB as a type III secretion system (T3SS) effector from Chromobacterium violaceum.
  • Investigating CipB's interaction with mitochondrial protein TUFM and autophagosomes via LC3-interacting region (LIR) motifs.
  • Utilizing a mouse model to assess the role of CipB in bacterial colonization and virulence.

Main Results:

  • CipB functions as an exogenous mitophagy receptor, targeting mitochondria and initiating the mitophagy-TFEB pathway.
  • CipB triggers TFEB nuclear translocation, suppresses proinflammatory cytokines, and promotes bacterial survival and pathogenesis.
  • CipB's mitophagy receptor activity is essential for Chromobacterium violaceum colonization in mouse liver and spleen.

Conclusions:

  • Bacterial pathogens can exploit host mitophagy via exogenous receptors like CipB to suppress immune responses.
  • CipB represents a conserved family of T3SS effectors that manipulate host mitophagy, highlighting a novel virulence strategy.
  • The mitophagy-TFEB axis is a potential target for therapeutic intervention against bacterial infections.

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