Needs Hope I, Protasoni Margherita, Henley Jeremy M, Prudent Julien, Collinson Ian, Pereira Gonçalo C
School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Medical Research Council-Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Life (Basel). 2021 May 11;11(5):432. doi: 10.3390/life11050432.
The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease.
超过99%的线粒体蛋白由核基因组编码并在细胞质中合成，这一事实使得线粒体蛋白导入过程成为正常细胞器生理学的基础。除此之外，核基因组包含呼吸复合体组装和功能所需的大部分蛋白质。这意味着如果没有功能完备的蛋白导入，线粒体呼吸将出现缺陷，细胞的主要ATP来源也会耗尽。当线粒体蛋白导入受损时，会激活一些应激反应途径，以克服功能障碍并恢复线粒体和细胞的蛋白质稳态。然而，线粒体蛋白导入长期受损以及随后呼吸链功能出现缺陷会导致包括原发性线粒体疾病和神经退行性变在内的多种疾病。本综述重点关注线粒体蛋白转运过程与呼吸复合体组装及功能是如何相互关联的、它们是如何被调控的，以及它们在健康和疾病中的重要性。
