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The integrated stress response in metabolic adaptation
1Department of Cell Biology, New York University Grossman School of Medicine, New York, New York, USA.
The Journal of Biological Chemistry
|March 10, 2024
Summary
The integrated stress response (ISR) uses stress-activated kinases to adapt to metabolic stress. This review covers ISR mechanisms, regulation of amino acid metabolism, and its role in disease.
Area of Science:
- Cellular Biology
- Molecular Biology
- Metabolic Regulation
Background:
- The integrated stress response (ISR) is a crucial cellular pathway.
- It is activated by stress-induced eIF2α kinases.
- ISR modulates gene expression to adapt to cellular stress.
Purpose of the Study:
- To review recent advances in understanding the ISR during metabolic stress adaptation.
- To discuss ISR activation mechanisms in response to amino acid and mitochondrial stress.
- To explore ISR's role in regulating amino acid metabolism and its impact on disease.
Main Methods:
- Literature review of recent scientific advances in ISR research.
- Analysis of signaling pathways involved in ISR activation.
- Examination of ISR's regulatory roles in metabolic pathways and disease models.
Main Results:
- ISR activation involves distinct eIF2α kinases responding to specific stresses.
- Stress-induced eIF2α phosphorylation attenuates global translation while enhancing specific mRNA translation.
- ISR plays a significant role in regulating amino acid metabolism.
Conclusions:
- Recent advances have significantly improved our understanding of ISR in metabolic stress.
- ISR is a key regulator of cellular adaptation to metabolic challenges.
- Dysregulation of ISR impacts various disease pathologies, highlighting its therapeutic potential.
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