Maity Sebabrata, Chakrabarti Oishee
Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 700064, India.
Homi Bhabha National Institute, India.
Biol Cell. 2021 Sep;113(9):375-400. doi: 10.1111/boc.202100002. Epub 2021 May 10.
Mitochondria are organelles involved in various functions related to cellular metabolism and homoeostasis. Though mitochondria contain own genome, their nuclear counterparts encode most of the different mitochondrial proteins. These are synthesised as precursors in the cytosol and have to be delivered into the mitochondria. These organelles hence have elaborate machineries for the import of precursor proteins from cytosol. The protein import machineries present in both mitochondrial membrane and aqueous compartments show great variability in pre-protein recognition, translocation and sorting across or into it. Mitochondrial protein import machineries also interact transiently with other protein complexes of the respiratory chain or those involved in the maintenance of membrane architecture. Hence mitochondrial protein translocation is an indispensable part of the regulatory network that maintains protein biogenesis, bioenergetics, membrane dynamics and quality control of the organelle. Various stress conditions and diseases that are associated with mitochondrial import defects lead to changes in cellular transcriptomic and proteomic profiles. Dysfunction in mitochondrial protein import also causes over-accumulation of precursor proteins and their aggregation in the cytosol. Multiple pathways may be activated for buffering these harmful consequences. Here, we present a comprehensive picture of import machinery and its role in cellular quality control in response to defective mitochondrial import. We also discuss the pathological consequences of dysfunctional mitochondrial protein import in neurodegeneration and cancer.
线粒体是参与细胞代谢和稳态相关各种功能的细胞器。尽管线粒体含有自身的基因组，但大多数不同的线粒体蛋白是由其细胞核中的对应基因编码的。这些蛋白在细胞质中以前体形式合成，必须被转运到线粒体中。因此，这些细胞器拥有复杂的机制来从细胞质中导入前体蛋白。存在于线粒体外膜和内膜间隙中的蛋白导入机制在蛋白前体的识别、转运以及跨膜或进入内膜间隙的分选过程中表现出很大的差异。线粒体蛋白导入机制还与呼吸链的其他蛋白复合物或参与维持膜结构的蛋白复合物发生短暂相互作用。因此，线粒体蛋白转运是维持细胞器蛋白质生物合成、生物能量学、膜动力学和质量控制的调控网络中不可或缺的一部分。与线粒体导入缺陷相关的各种应激条件和疾病会导致细胞转录组和蛋白质组图谱的变化。线粒体蛋白导入功能障碍还会导致前体蛋白在细胞质中过度积累及其聚集。可能会激活多种途径来缓冲这些有害后果。在此，我们全面介绍了导入机制及其在应对线粒体导入缺陷时在细胞质量控制中的作用。我们还讨论了线粒体蛋白导入功能障碍在神经退行性疾病和癌症中的病理后果。
