近日，美国加州理工学院教授Shu-ou Shan及其小组的最新研究提出了共译线粒体蛋白输入的原理。该研究于2025年8月11日发表于国际一流学术期刊《细胞》杂志上。

使用选择性核糖体分析，研究组发现近20%的线粒体蛋白可以在人类细胞中共翻译导入。共翻译输入需要新生蛋白上的N端序列，并有助于线粒体表面的局部翻译。该途径不支持膜蛋白，而是优先考虑大的、多结构域的、拓扑复杂的蛋白质，当共翻译靶向时，其输入效率提高。与协同翻译蛋白靶向内质网（ER）的早期发作相反，线粒体蛋白上的前序在翻译过程中被抑制，直到一个大的球状结构域从核糖体中出现才开始靶向。他们的发现揭示了一种多层蛋白质分类策略，该策略控制着线粒体蛋白质靶向的时间和特异性。

研究人员表示，几乎所有的线粒体蛋白都在细胞质核糖体上翻译。这些蛋白质随后是如何被运送到线粒体的，目前还不清楚。

附：英文原文

Title: Principles of cotranslational mitochondrial protein import

Author: Zikun Zhu, Saurav Mallik, Taylor A. Stevens, Riming Huang, Emmanuel D. Levy, Shu-ou Shan

Issue&Volume: 2025-08-11

Abstract: 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.

DOI: 10.1016/j.cell.2025.07.021

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00811-6