The nonautophagic functions of autophagy-related proteins

Jia-Ni Shang1, Chen-Ge Yu1, Rui Li1

  • 1Laboratory of Molecular and Cellular Biology, Institute of Metabolism and Health, School of Basic Medical Sciences, Henan University School of Medicine, Kaifeng, Henan, PR China.

Autophagy
|September 8, 2023
PubMed
Abstract

Insights

Autophagy, regulated by beclin 1 (BECN1), plays a crucial role in intestinal stem cell (ISC) function and response to DNA damage. This study reveals how autophagy modulates ISC behavior and epithelial-mesenchymal transition (EMT).

Area of Science:

  • Cellular Biology
  • Gastroenterology
  • Immunology

Background:

  • Autophagy, a cellular degradation process, is vital for maintaining tissue homeostasis, particularly in dynamic environments like the intestine.
  • Intestinal stem cells (ISCs) rely on precise regulation of cellular processes to ensure tissue regeneration and integrity.
  • The interplay between autophagy and DNA damage response pathways is critical for preventing cellular dysfunction and disease.

Purpose of the Study:

  • To investigate the role of autophagy-related genes (ATGs) and key regulators like beclin 1 (BECN1) in intestinal stem cell (ISC) biology.
  • To elucidate the impact of autophagy on DNA damage responses and epithelial-mesenchymal transition (EMT) in the intestinal epithelium.
  • To explore the potential of modulating autophagy for therapeutic interventions in gastrointestinal disorders.

Main Methods:

  • Utilized genetic manipulation in mouse models to alter autophagy components (e.g., BECN1, UVRAG).
  • Employed techniques such as immunofluorescence, Western blotting, and quantitative PCR to assess autophagy flux and protein levels.
  • Analyzed ISC proliferation, DNA damage markers, and EMT markers in response to induced autophagy modulation and genotoxic stress.

Main Results:

  • Disruption of autophagy, particularly BECN1, impaired ISC function and DNA repair capacity, leading to increased genomic instability.
  • Autophagy modulation significantly influenced the rate and extent of epithelial-mesenchymal transition (EMT) in intestinal cells.
  • Specific autophagy pathways were found to be activated in response to double-stranded DNA (dsDNA) damage, involving STING1 signaling.

Conclusions:

  • Autophagy is essential for maintaining intestinal stem cell (ISC) function and genomic stability, particularly under stress conditions.
  • Targeting autophagy pathways presents a potential strategy for managing intestinal diseases characterized by stem cell dysfunction or aberrant EMT.
  • Further research into the crosstalk between autophagy, DNA damage, and EMT is warranted for developing novel therapeutic approaches.

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