Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, D-37075 Göttingen, Germany.
Biol Chem. 2023 Jun 29;404(8-9):769-779. doi: 10.1515/hsz-2023-0127. Print 2023 Jul 26.
Mitochondria are the essential players in eukaryotic ATP production by oxidative phosphorylation, which relies on the maintenance and accurate expression of the mitochondrial genome. Even though the basic principles of translation are conserved due to the descendance from a bacterial ancestor, some deviations regarding translation factors as well as mRNA characteristics and the applied genetic code are present in human mitochondria. Together, these features are certain challenges during translation the mitochondrion has to handle. Here, we discuss the current knowledge regarding mitochondrial translation focusing on the termination process and the associated quality control mechanisms. We describe how mtRF1a resembles bacterial RF1 mechanistically and summarize and recent data leading to the conclusion of mtRF1a being the major mitochondrial release factor. On the other hand, we discuss the ongoing debate about the function of the second codon-dependent mitochondrial release factor mtRF1 regarding its role as a specialized termination factor. Finally, we link defects in mitochondrial translation termination to the activation of mitochondrial rescue mechanisms highlighting the importance of ribosome-associated quality control for sufficient respiratory function and therefore for human health.
线粒体是真核生物通过氧化磷酸化产生 ATP 的关键参与者，这依赖于线粒体基因组的维持和准确表达。尽管由于起源于细菌祖先，翻译的基本原则是保守的，但在翻译因子以及 mRNA 特征和应用的遗传密码方面，人类线粒体存在一些偏差。这些特征共同构成了线粒体翻译过程中必须应对的一些挑战。在这里，我们讨论了关于线粒体翻译的最新知识，重点是终止过程和相关的质量控制机制。我们描述了 mtRF1a 在机制上如何类似于细菌 RF1，并总结了最近的数据，这些数据得出结论，mtRF1a 是主要的线粒体释放因子。另一方面，我们讨论了关于第二种依赖于密码子的线粒体释放因子 mtRF1 的功能的持续争论，即其作为一种专门的终止因子的作用。最后，我们将线粒体翻译终止缺陷与线粒体拯救机制的激活联系起来，突出了核糖体相关质量控制对于充分的呼吸功能，进而对于人类健康的重要性。
