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Updated: Dec 6, 2025

Live Cell Imaging during Mechanical Stretch
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Live Cell Imaging during Mechanical Stretch

Published on: August 19, 2015

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Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the

Ren Jing1,2, Zhao-Kun Hu1,2, Fei Lin1,2

  • 1Department of Anesthesiology, Guangxi Medical University Affiliated Tumor Hospital & Oncology Medical College, Nanning, China.

Frontiers in Cell and Developmental Biology
|October 5, 2020
PubMed
Abstract

Insights

Phosphatase and tensin homolog-induced kinase 1 (PINK1)-dependent mitophagy releases mitochondrial DNA, activating Toll-like receptor 9 (TLR9) and causing lung injury. Inhibiting this pathway may prevent ventilation-induced lung inflammation.

Area of Science:

  • Cell Biology
  • Immunology
  • Pulmonary Medicine

Background:

  • Mitophagy-induced mitochondrial damage and DNA release trigger inflammation in ventilation-induced lung injury models.
  • The precise mechanism linking mitophagy, mitochondrial DNA release, and inflammation remains unclear.

Purpose of the Study:

  • To elucidate the role of phosphatase and tensin homolog-induced kinase 1 (PINK1)-mediated mitophagy in mitochondrial DNA release and subsequent inflammation in lung epithelial cells subjected to cyclic stretching (CS).
  • To investigate the involvement of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) in the CS-induced inflammatory response.

Main Methods:

  • Established a cell culture model of CS-induced lung epithelial cell injury.
  • Utilized lentivirus transfection for genetic manipulation of PINK1 expression.
  • Employed pharmacological inhibitors for TLR9 and MyD88.
  • Administered exogenous mitochondrial DNA (mtDNA) to verify its role in the inflammatory response.

Main Results:

  • Knocking down PINK1 reduced mitophagy, mtDNA release, inflammation, and injury in CS-exposed lung cells.
  • Upregulating PINK1 or TLR9 exacerbated CS-induced inflammation and injury, involving MyD88 and nuclear factor-κB (NF-κB)/p65.
  • Downregulating MyD88 protected cells from CS injury and reduced NF-κB/p65 expression.

Conclusions:

  • PINK1-dependent mitophagy and subsequent mtDNA release activate the TLR9/MyD88/NF-κB pathway, contributing significantly to stretch-induced lung epithelial cell injury.
  • Targeting this pathway, particularly PINK1-mediated mitophagy and TLR9 activation, presents a potential therapeutic strategy for preventing inflammation and cell injury in mechanically ventilated patients.
Keywords:
Toll-like receptor 9lung injurymechanical stretchingmitochondrial DNAmitophagy

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