RRC ID 58401
Author Li X, Wu J, Sun X, Wu Q, Li Y, Li K, Zhang Q, Li Y, Abel ED, Chen H.
Title Autophagy Reprograms Alveolar Progenitor Cell Metabolism in Response to Lung Injury.
Journal Stem Cell Reports
Abstract Autophagy is a protective cellular mechanism in response to stress conditions. However, whether autophagy is required for maintenance of the alveolar epithelium is unknown. Here, we report that the loss of autophagy-related 5 (Atg5) in AT2 cells worsened bleomycin-induced lung injury. Mechanistically, during bleomycin injury, autophagy downregulated lipid metabolism but upregulated glucose metabolism in AT2 cells for alveolar repair. Chemical blockade of fatty acid synthesis promoted organoid growth of AT2 cells and counteracted the effects of autophagy loss on bleomycin injury. However, genetic loss of glucose transporter 1, interference with glycolysis, or interference with the pentose phosphate pathway reduced the proliferation of AT2 cells. Inhibition of glucose metabolism exacerbated the effects of bleomycin injury. Failure of autophagy generated additional hydrogen peroxide, which reduced AT2 cell proliferation. These data highlight an essential role for autophagy in reprogramming the metabolism of alveolar progenitor cells to meet energy needs for alveolar epithelial regeneration.
Volume 14(3)
Pages 420-432
Published 2020-3-10
DOI 10.1016/j.stemcr.2020.01.008
PII S2213-6711(20)30029-1
PMID 32059792
PMC PMC7066233
MeSH Alveolar Epithelial Cells / metabolism* Alveolar Epithelial Cells / pathology* Animals Autophagy* Bleomycin Cell Proliferation Cellular Reprogramming* Fatty Acids / biosynthesis Glucose Transporter Type 1 / metabolism Glycolysis Hydrogen Peroxide / metabolism Lung Injury / metabolism* Lung Injury / pathology* Mice, Inbred C57BL Oxidative Stress Pentose Phosphate Pathway Stem Cells / metabolism*
IF 6.032
Times Cited 0
Mice RBRC02975