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Updated: Dec 18, 2025
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Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
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Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy
Juliette Humeau1,2,3, Marion Leduc1,2, Giulia Cerrato1,2,3
1Equipe Labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Paris, France.
Cell Death & Disease
|June 10, 2020
Summary
The integrated stress response involves eukaryotic initiation factor-2α (eIF2α) phosphorylation. This study shows eIF2α phosphorylation is essential for inducing autophagy, a key cellular process.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The integrated stress response (ISR) is a cellular defense mechanism.
- ISR is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) at serine 51.
- eIF2α phosphorylation is mediated by one of four specific kinases (EIF2AK1-4).
Purpose of the Study:
- To investigate the role of eIF2α phosphorylation in the induction of autophagy.
- To determine if pharmacological agents inducing autophagy require eIF2α phosphorylation.
Main Methods:
- Monitoring autophagic puncta formation.
- Utilizing cells with a non-phosphorylable eIF2α mutant (S51A).
- Employing cells deficient in all four eIF2α kinases.
- Inhibiting eIF2α phosphatases.
Main Results:
- Autophagy induction by various compounds correlated with eIF2α phosphorylation.
- Autophagy modulation was partially inhibited in eIF2α mutant or kinase-deficient cells.
- Distinct kinases were implicated in responses to different autophagy inducers.
- Inhibition of eIF2α phosphatases stimulated autophagy.
Conclusions:
- eIF2α phosphorylation is a central event required for autophagy stimulation.
- The findings highlight a conserved mechanism linking the integrated stress response to autophagy induction.
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