Related Experiment Video
Updated: Jun 6, 2026
10:36
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Atg8 orchestrates stress-responsive chromatin programs across immunity and metabolism
Kevin P Kelly1, Navyashree A Ramesh1, Sunidhi Ranganathan1
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Biorxiv : the Preprint Server for Biology
|June 5, 2026
Summary
Autophagy protein Atg8/LC3 acts as a nuclear cofactor, coordinating immune and metabolic gene transcription during stress. This reveals a new role for autophagy machinery in integrating diverse cellular stress responses.
Area of Science:
- Cellular Biology
- Molecular Biology
- Genetics
Background:
- Organisms must coordinate transcriptional responses to immune and metabolic stress.
- Adipose tissue integrates these signals, mounting antimicrobial defense and remodeling lipid metabolism.
- The molecular machinery coordinating these dual functions is incompletely understood.
Purpose of the Study:
- To investigate the non-canonical roles of Atg8/LC3 in nuclear gene regulation beyond autophagy.
- To determine if Atg8 contributes to stress-coordinated transcription in response to immune and metabolic challenges.
- To elucidate the molecular mechanisms by which Atg8 integrates immune and metabolic stress responses.
Main Methods:
- Unbiased CUT&RUN in adult Drosophila nuclei to map Atg8 chromatin occupancy.
- CRISPR engineering to create AIM-mutant Dif flies.
- Analysis of fly susceptibility to infection and high-sugar diet (HSD).
- Assessment of Dif nuclear accumulation under stress conditions.
Main Results:
- Endogenous Atg8 exhibits broad chromatin occupancy at immune, metabolic, and autophagy loci.
- Atg8 accumulates in nuclei under prolonged HSD and acute Gram-positive infection.
- Two conserved Atg8-interacting motifs (AIMs) in NF-κB/Dif are essential for fly survival under stress.
- AIM-mutant Dif shows impaired infection-induced nuclear accumulation, indicating Atg8's role in Dif shuttling and function.
- Atg8 acts as a stress-responsive chromatin cofactor for immune and metabolic transcription.
Conclusions:
- Atg8/LC3 has non-canonical roles in nuclear gene regulation, extending beyond canonical autophagy.
- Autophagy machinery contributes to stress-specific transcriptional complex assembly.
- Atg8-mediated coordination of immune and metabolic transcription is a general principle for integrating diverse stress signals.
- Findings have implications for obesity, chronic inflammation, and diseases involving immune and metabolic dysregulation.
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