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eIF5A controls mitoprotein import by relieving ribosome stalling at the TIM50 translocase mRNA
Marina Barba-Aliaga1,2, Vanessa Bernal1,2, Cynthia Rong3
1Instituto de Biotecnología y Biomedicina (Biotecmed), Universitat de València, 46100 València, Spain.
Biorxiv : the Preprint Server for Biology
|January 8, 2024
Summary
The translation factor eIF5A (eukaryotic initiation factor 5A) aids mitochondrial protein import by preventing ribosome stalling during the synthesis of key mitochondrial proteins like Tim50.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitochondrial function relies on efficient import of nuclear-encoded proteins.
- The translation factor eIF5A (eukaryotic initiation factor 5A) is known to affect mitochondrial function, but the mechanism is unclear.
- eIF5A resolves ribosome stalling at specific amino acid sequences, particularly polyprolines.
Approach:
- Depleted eIF5A in yeast and observed effects on protein translation and mitochondrial import.
- Identified Tim50, a component of the TIM23 translocase, as a direct eIF5A target.
- Investigated the role of polyproline sequences in Tim50 mRNA translation and mitochondrial import.
Key Points:
- eIF5A depletion reduces TCA cycle and oxidative phosphorylation proteins.
- Loss of eIF5A causes accumulation of cytosolic protein precursors and induces mitochondrial import stress.
- eIF5A directly facilitates Tim50 translation by resolving ribosome stalling on its mRNA.
Conclusions:
- eIF5A is essential for efficient mitochondrial protein import by resolving ribosome stalling.
- This mechanism ensures proper mitochondrial function and biogenesis.
- Targeting polyproline-rich sequences in mRNA translation is a key regulatory point for mitochondrial health.
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