Autophagy Mechanisms in Acute Lung Injury

Acute lung injury (ALI) arises from diverse insults—sepsis, chemical exposure or trauma—that compromise the alveolar–capillary barrier and provoke intense inflammation. Autophagy, a conserved process of lysosomal degradation, plays a dual role in ALI by removing damaged organelles and protein aggregates, thus limiting oxidative stress and supporting cell survival. In alveolar macrophages and type II epithelial cells, selective autophagy of mitochondria (mitophagy) curbs reactive oxygen species and prevents aberrant activation of inflammasomes. The dynamic progression from autophagosome formation to lysosomal clearance—termed autophagic flux—is finely tuned by signalling networks such as the PI3K/AKT/mTOR axis and the cGAS-STING pathway. When balanced, autophagy mitigates apoptosis and preserves epithelial integrity; when excessive or stalled, it may aggravate cell death and barrier dysfunction. Understanding this balance is essential to harness autophagy as a therapeutic avenue, with the aim of restoring alveolar homeostasis, reducing inflammation and improving clinical outcomes in ALI.

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Autophagy Mechanisms in Acute Lung Injury publication trend

The graph below shows the total number of articles in autophagy mechanisms in acute lung injury across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: A cellular process that delivers cytoplasmic cargo to lysosomes for degradation and recycling.

Autophagic flux: The complete sequence of autophagy, from autophagosome formation to lysosomal breakdown of contents.

Mitophagy: Selective autophagy of damaged or superfluous mitochondria to maintain mitochondrial quality.

Inflammasome: A multi-protein complex that activates inflammatory cytokines and pyroptotic cell death.

PI3K/AKT/mTOR pathway: A central signalling cascade that regulates cell growth, metabolism and autophagy.

GPR109α: A G-protein-coupled receptor that mediates immune responses and can trigger autophagy upon activation.

References

1. Liensinine alleviates LPS-induced acute lung injury by blocking autophagic flux via PI3K/AKT/mTOR signaling pathway. Biomedicine & Pharmacotherapy (2023).
2. 3-Hydroxybutyrate ameliorates sepsis-associated acute lung injury by promoting autophagy through the activation of GPR109α in macrophages. Biochemical Pharmacology (2023).
3. RAGE inhibition alleviates lipopolysaccharides-induced lung injury via directly suppressing autophagic apoptosis of type II alveolar epithelial cells. Respiratory Research (2023).
4. Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury. Cell Death & Disease (2021).