Microsporidian Encephalitozoon hellem inhibits host mitophagy by inducing ERAD to degrade BNIP3L

Ziyun Zou1,2, Yibo Hu1,2, Zhongxia Guan1,2

  • 1State Key Laboratory of Resource Insects, Southwest University, Chongqing, China.

Plos Pathogens
|March 23, 2026
PubMed

Insights

Microsporidia pathogens like Encephalitozoon hellem disrupt host mitophagy. The secreted protein EhPTP4 manipulates endoplasmic reticulum-associated degradation (ERAD) and histone acetylation to suppress this vital cellular process.

Area of Science:

  • Cellular Biology
  • Pathogen-Host Interactions
  • Molecular Biology

Background:

  • Microsporidia are intracellular pathogens impacting host mitochondrial function.
  • Understanding microsporidian manipulation of host cell degradation pathways is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To elucidate the novel mechanism by which Encephalitozoon hellem disrupts host mitophagy.
  • To identify key effectors and molecular pathways involved in microsporidian pathogenesis.

Main Methods:

  • Localization studies of the secreted protein EhPTP4.
  • Analysis of endoplasmic reticulum-associated degradation (ERAD) pathway components.
  • Investigation of protein ubiquitination and mitophagy regulators.
  • Molecular interaction network analysis including histone acetylation.

Main Results:

  • The secreted protein EhPTP4 localizes to the nucleus and upregulates ERAD components (HSPA5, HERPUD1, PDIA4).
  • EhPTP4 induces protein ubiquitination, leading to the degradation of BNIP3L, a mitophagy regulator.
  • EhPTP4 interacts with RCOR1 and histone H3, modulating histone H3K14ac and further influencing HERPUD1 expression.

Conclusions:

  • Microsporidia employ a sophisticated strategy involving ER stress response and histone acetylation to suppress host mitophagy.
  • EhPTP4 is a key effector in this process, highlighting a novel mechanism of microsporidian pathogenesis.

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