eIF3 Orchestrates a Biphasic Stress Response Linking Translational Control to Mitochondrial Integrity in Skeletal Muscle - PubMed
3 hours ago
- #mitochondrial integrity
- #eIF3
- #skeletal muscle stress
- eIF3 is identified as a key regulator in skeletal muscle stress responses, coordinating translation and mitochondrial function.
- Two mouse models reveal biphasic eIF3 dynamics: dexamethasone-induced atrophy broadly downregulates eIF3 subunits and impairs mitochondrial ETC, while acute training selectively reduces some subunits but preserves eIF3f and adaptively remodels ETC.
- eIF3 differs from other translation factors like eIF2α, as its dysregulation selectively affects mitochondrial protein synthesis rather than causing global translation suppression.
- Knockdown of eIF3e or eIF3f in C2C12 myotubes shows distinct effects on mitochondrial proteins and atrophy signaling, with eIF3f knockdown leading to more severe mitochondrial protein suppression.
- eIF3 subunit loss directly reduces mitochondrial oxygen consumption and attenuates global protein synthesis, while also suppressing mTORC1 signaling and modulating ubiquitin-proteasome activity without affecting bulk autophagy.
- The study positions eIF3 as a molecular integrator linking translational control to mitochondrial integrity, highlighting its potential as a therapeutic target for muscle adaptation and wasting disorders.