Mitophagy in Pulmonary Fibrosis: Molecular Interactions, Hypoxia Interactions, and Therapeutic Strategies

Area of Science:

• Cell Biology
• Pulmonary Medicine
• Molecular Biology

Background:

• Mitophagy, the selective degradation of damaged mitochondria, is crucial for cellular homeostasis.
• Dysfunctional mitophagy contributes to pulmonary fibrosis (PF) pathogenesis through mitochondrial damage, oxidative stress, and cellular senescence.
• This dysfunction creates a cycle of autophagy inhibition and fibrosis activation, accelerating PF progression.

Purpose of the Study:

• To systematically review the molecular regulatory network of mitophagy in pulmonary fibrosis.
• To explore the interaction between mitophagy and hypoxia-responsive pathways in PF.
• To discuss current and emerging therapeutic strategies targeting mitophagy for PF treatment.

Main Methods:

• Systematic literature review of mitophagy's role in pulmonary fibrosis.
• Analysis of molecular mechanisms linking mitophagy defects to fibrotic processes.
• Evaluation of therapeutic interventions targeting mitophagy pathways.

Main Results:

• Defective mitophagy leads to accumulation of damaged mitochondria, increased mitochondrial ROS (mtROS), ferroptosis, and senescence.
• These events promote fibroblast activation and excessive extracellular matrix deposition in PF.
• Hypoxia-responsive pathways interact with mitophagy, exacerbating PF pathogenesis.

Conclusions:

• Targeting mitophagy presents a promising therapeutic avenue for pulmonary fibrosis.
• Small molecules, natural compounds, gene therapy, and nanocarriers show potential for activating mitophagy and treating PF.
• Challenges include achieving cell-type specificity, managing dynamic thresholds, and ensuring efficient delivery for effective PF treatment.