2025-08-29 カリフォルニア工科大学(Caltech)
Shan and her colleagues found that nearly 20 percent of mitochondrial proteins can be imported during translation, after the ribosome has made the protein’s first large domain.Credit: The Shan Lab/Caltech
<関連情報>
- https://www.caltech.edu/about/news/caltech-biochemists-uncover-new-rules-of-mitochondrial-protein-import
- https://www.cell.com/cell/fulltext/S0092-8674(25)00811-6
翻訳同時型ミトコンドリアタンパク質輸入の原理 Principles of cotranslational mitochondrial protein import
Zikun Zhu ∙ Saurav Mallik ∙ Taylor A. Stevens ∙ Riming Huang ∙ Emmanuel D. Levy, ∙ Shu-ou Shan
Cell Published:August 11, 2025
DOI:https://doi.org/10.1016/j.cell.2025.07.021
Highlights
- Selective ribosome profiling reveals the cotranslational interactome of the TOM complex
- Cotranslational import prioritizes large mitochondrial proteins with complex topology
- An N-terminal presequence is necessary but insufficient for import during translation
- Emergence of a large globular domain allows the initiation of cotranslational import
Summary
Nearly all mitochondrial proteins are translated on cytosolic ribosomes. How these proteins are subsequently delivered to mitochondria remains poorly understood. Using selective ribosome profiling, we show that nearly 20% of mitochondrial proteins can be imported cotranslationally in human cells. Cotranslational import requires an N-terminal presequence on the nascent protein and contributes to localized translation at the mitochondrial surface. This pathway does not favor membrane proteins but instead prioritizes large, multi-domain, topologically complex proteins, whose import efficiency is enhanced when targeted cotranslationally. In contrast to the early onset of cotranslational protein targeting to the endoplasmic reticulum (ER), the presequence on mitochondrial proteins is inhibited from initiating targeting early during translation until a large globular domain emerges from the ribosome. Our findings reveal a multi-layered protein sorting strategy that controls the timing and specificity of mitochondrial protein targeting.
