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Updated: Jun 12, 2026
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Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
Published on: December 25, 2021
eIF3 Orchestrates a Biphasic Stress Response Linking Translational Control to Mitochondrial Integrity in Skeletal
Yingying Lin1,2,3,4,5, Jianing Xia4,5, Man Li6
1Otolaryngology & Head and Neck Center, Zhejiang Provincial People's Hospital, Hangzhou, China.
Summary
Skeletal muscle stress impacts protein synthesis and mitochondria differently based on the stressor. Eukaryotic initiation factor 3 (eIF3) subunits show distinct responses, influencing mitochondrial function and offering therapeutic targets.
Area of Science:
- Molecular Biology
- Cellular Biology
- Physiology
Background:
- Skeletal muscle adaptation relies on protein synthesis and mitochondrial function.
- Canonical translation regulators like eIF2α and 4E-BP1 are studied, but eukaryotic initiation factor 3 (eIF3) roles in muscle stress are unclear.
- eIF3 regulates translation and mitochondrial homeostasis, but subunit-specific responses to stress are unknown.
Purpose of the Study:
- To characterize eIF3 dynamics and mitochondrial function under distinct skeletal muscle stress conditions.
- To investigate the differential responses of eIF3 subunits to exhaustive exercise and dexamethasone-induced atrophy.
- To elucidate the role of eIF3 in linking translation control to mitochondrial integrity.
Main Methods:
- Systematic characterization of eIF3 dynamics and mitochondrial function in mouse models.
- Acute exhaustive training and dexamethasone (DEX)-induced atrophy models.
- Integrated proteomic, transcriptomic, imaging, siRNA knockdown, Seahorse XF, SUnSET assays, and Western blotting.
Main Results:
- DEX treatment broadly downregulated eIF3 subunits and impaired mitochondrial electron transport chain (ETC).
- Acute training selectively decreased some eIF3 subunits but preserved eIF3f, alongside adaptive ETC remodeling.
- eIF3 subunit loss impaired mitochondrial oxygen consumption, global protein synthesis, and mTORC1 signaling, with eIF3f knockdown causing severe mitochondrial protein suppression.
Conclusions:
- eIF3 exhibits biphasic regulatory patterns in response to distinct muscle stressors, differentiating it from other translation factors.
- eIF3 acts as a molecular integrator of translational control and mitochondrial integrity in skeletal muscle.
- eIF3 subunits, particularly eIF3f, are potential therapeutic targets for muscle adaptation and wasting disorders.
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