Luo Ying, Bähler Jürg, Huang Ying
Jiangsu Key Laboratory for Microbes and Genomics, School of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China.
Institute of Healthy Ageing, Department of Genetics, Evolution & Environment, University College London, London WC1E 6BT, UK.
Biomolecules. 2025 May 10;15(5):695. doi: 10.3390/biom15050695.
Translation initiation in mitochondria involves unique mechanisms distinct from those in the cytosol or in bacteria. The mitochondrial translation initiation factor 2 (Mti2) is the ortholog of human MTIF2, which plays a vital role in synthesizing proteins in mitochondria. Here, we investigate the insertion domain of Mti2, which stabilizes its interaction with the ribosome and is crucial for efficient translation initiation. Our results show that the insertion domain is critical for the proper folding and function of Mti2. The absence of the insertion domain disrupts cell growth and affects the expression of genes encoded by mitochondrial DNA. Additionally, we show that Mti2 physically interacts with the small subunits of mitoribosomes (mtSSU), and deletion of the insertion domain dissociates mitochondrial initiation factors from the mitoribosome, reducing the efficiency of mitochondrial translation. Altogether, these findings highlight the conserved role of the insertion domain in facilitating translation initiation in fission yeast and thus reveal shared principles of mitochondrial translation initiation in both fission yeast and humans.
线粒体中的翻译起始涉及独特的机制，这些机制不同于胞质溶胶或细菌中的机制。线粒体翻译起始因子2（Mti2）是人类MTIF2的直系同源物，它在在线粒体中合成蛋白质中起着至关重要的作用。在这里，我们研究了Mti2的插入结构域，该结构域稳定了其与核糖体的相互作用，对于有效的翻译起始至关重要。我们的结果表明，插入结构域对于Mti2的正确折叠和功能至关重要。插入结构域的缺失会破坏细胞生长并影响线粒体DNA编码的基因的表达。此外，我们表明Mti2与线粒体核糖体的小亚基（mtSSU）发生物理相互作用，插入结构域的缺失会使线粒体起始因子与线粒体核糖体解离，从而降低线粒体翻译的效率。总之，这些发现突出了插入结构域在促进裂殖酵母中翻译起始方面的保守作用，从而揭示了裂殖酵母和人类中线粒体翻译起始的共同原则。
