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Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
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MAPK15-ULK1 signaling regulates mitophagy of airway epithelial cell in chronic obstructive pulmonary disease

Ming Zhang1, Lei Fang2, Liang Zhou2

  • 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Pulmonary Cell Research & Clinic of Respiratory Medicine, Dept. Biomedicine University of Basel & University Hospital of Basel, CH-4031, Basel, Switzerland.

Free Radical Biology & Medicine
|July 5, 2021
PubMed

Insights

Cigarette smoke activates MAPK15-ULK1 signaling in airway cells, increasing mitophagy and oxidative stress. This pathway is active in chronic obstructive pulmonary disease (COPD) and may offer a new therapeutic target.

Area of Science:

  • Cellular Biology
  • Respiratory Medicine
  • Molecular Pathology

Background:

  • Mitochondrial damage and oxidative stress in airway epithelium are key features of chronic obstructive pulmonary disease (COPD).
  • Mitophagy, a cellular process for removing damaged mitochondria, is regulated by MAPK15-ULK1 signaling, but its role in COPD remains unclear.

Purpose of the Study:

  • To investigate the role of MAPK15-ULK1 signaling in the airway epithelium of COPD patients.
  • To determine if cigarette smoke extract (CSE) activates MAPK15-ULK1 signaling in human airway epithelial cells.

Main Methods:

  • Examined MAPK15-ULK1 signaling, mitophagy markers (Beclin1, LC3II/LC3I ratio), and mitochondrial oxidative stress in airway epithelial cells from COPD patients and controls.
  • Exposed human airway epithelial cells to CSE and analyzed the effects on MAPK15-ULK1 signaling and mitophagy.
  • Utilized siRNA to silence MAPK15 or ULK1 to assess their impact on CSE-induced mitophagy and cell viability.

Main Results:

  • Increased phosphorylation of MAPK15 and ULK1 (Ser555), along with elevated Beclin1 and LC3II/LC3I ratio, were observed in COPD airway epithelium.
  • CSE exposure significantly upregulated MAPK15-ULK1 signaling, Beclin1, and LC3II/LC3I ratio in a dose- and time-dependent manner.
  • MAPK15-ULK1 signaling inhibition via siRNA reduced CSE-induced mitophagy and mitochondrial oxidative stress, improving cell viability.

Conclusions:

  • Cigarette smoke activates the MAPK15-ULK1 pathway in airway epithelial cells, promoting mitophagy and mitochondrial oxidative stress.
  • This signaling pathway is dysregulated in COPD airway epithelial cells.
  • The MAPK15-ULK1 pathway represents a potential therapeutic target for COPD treatment.
Keywords:
Airway epithelial cellChronic obstructive pulmonary diseaseMAPK15MitophagyULK1

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