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β-Catenin Elicits Drp1-Mediated Mitochondrial Fission Activating the Pro-Apoptotic Caspase-1/IL-1β Signalosome in

Shagun Sharma1, Manmohan Kumar1, Jai Kumar1

  • 1Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi 110007, India.

Cells
|June 10, 2023
PubMed

Insights

Canonical Wnt signaling activates apoptosis in zebrafish kidney macrophages during Aeromonas hydrophila infection. This pathway promotes mitochondrial fission and bacterial clearance, revealing a host-centric role in pathogenesis.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbial Pathogenesis

Background:

  • Canonical Wnt signaling is crucial in microbial pathogenesis, but its role in Aeromonas hydrophila (A. hydrophila) infection remains unclear.
  • Understanding host-pathogen interactions is vital for developing effective therapeutic strategies against bacterial infections.

Purpose of the Study:

  • To investigate the involvement of the canonical Wnt signaling pathway in A. hydrophila infection.
  • To elucidate the role of β-catenin in the host response to A. hydrophila infection.

Main Methods:

  • Utilized zebrafish (Danio rerio) kidney macrophages (ZKM) to study gene expression changes.
  • Assessed protein accumulation and employed a β-catenin specific inhibitor (JW67).
  • Analyzed reactive oxygen species (ROS) production, mitochondrial membrane potential, and mitochondrial fission.

Main Results:

  • A. hydrophila infection upregulated key Wnt signaling components (wnt2, wnt3a, fzd5, lrp6, β-catenin) and decreased inhibitory factors (gsk3b, axin) in ZKM.
  • Increased nuclear β-catenin promoted apoptosis via NADPH oxidase-mediated ROS and sustained mitochondrial ROS generation.
  • β-catenin induced mitochondrial fission, leading to caspase-3 activation, ZKM apoptosis, and bacterial clearance.

Conclusions:

  • Canonical Wnt signaling, specifically β-catenin, plays a host-centric role in A. hydrophila pathogenesis.
  • β-catenin activation of mitochondrial fission machinery promotes ZKM apoptosis and bacterial containment.
  • This study highlights a novel mechanism of host defense involving Wnt signaling and mitochondrial dynamics.
Keywords:
A. hydrophilaNOXapoptosismtROSzebrafish kidney macrophagesβ-catenin

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