Chlamydia trachomatis plasmid-encoded protein pORF5 protects mitochondrial function by inducing mitophagy and increasing HMGB1 expression
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Wenbo Lei1, Qun Li1, Shengmei Su1
1Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, No. 28, Changsheng West Road Hengyang, Hunan 421001, P.R. China.
Abstract:
Chlamydia trachomatis, an obligate intracellular pathogen, has various effective strategies to regulate host cell death signalling pathways that ensure completion of their growth cycle. Mitochondrial autophagy (mitophagy) is responsible for elimination of dysfunctional and impaired mitochondria, and this process plays a critical role in cell survival via restriction of the mitochondrial apoptotic pathway. However, the specific molecular mechanisms are not entirely understood. In the present study, we observed that pORF5 plasmid protein of C. trachomatis plays a crucial role in attenuating mitochondrial dysfunction and apoptosis. Knockdown high mobility group box 1 (HMGB1) by lentivirus suppressed pORF5-induced mitophagy and increased apoptosis, implying that pORF5 may participate in cell death signalling pathways via up-regulation of HMGB1. Thus, we concluded that up-regulation of HMGB1 is a pivotal event for C. trachomatis that manipulates mitophagy and apoptosis in order to establish a favourable environment supportive of Chlamydial growth, which should further promote our understanding of Chlamydial pathogenic mechanisms.
Insights
Chlamydia trachomatis uses the pORF5 protein to up-regulate High Mobility Group Box 1 (HMGB1), manipulating mitochondrial autophagy (mitophagy) and apoptosis for pathogen survival and growth.
Area of Science:
- Microbiology
- Cell Biology
- Pathogen-Host Interactions
Background:
- Chlamydia trachomatis manipulates host cell death pathways for its lifecycle.
- Mitochondrial autophagy (mitophagy) eliminates damaged mitochondria, preventing apoptosis and promoting cell survival.
- The precise mechanisms by which Chlamydia regulates mitophagy and apoptosis are not fully understood.
Purpose of the Study:
- To investigate the role of Chlamydia trachomatis pORF5 protein in regulating host cell death.
- To elucidate the involvement of High Mobility Group Box 1 (HMGB1) in Chlamydia-mediated manipulation of mitophagy and apoptosis.
Main Methods:
- Utilized plasmid protein pORF5 from C. trachomatis.
- Employed lentivirus-mediated knockdown of High Mobility Group Box 1 (HMGB1).
- Assessed mitophagy and apoptosis levels in infected host cells.
Main Results:
- The pORF5 protein of C. trachomatis was found to attenuate mitochondrial dysfunction and apoptosis.
- Knockdown of HMGB1 inhibited pORF5-induced mitophagy and exacerbated apoptosis.
- These findings suggest pORF5 influences cell death pathways through HMGB1 up-regulation.
Conclusions:
- Up-regulation of HMGB1 is a key mechanism employed by C. trachomatis.
- This manipulation of HMGB1 controls mitophagy and apoptosis, creating a favorable environment for Chlamydial growth.
- Understanding this interaction enhances knowledge of Chlamydial pathogenesis.