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.

中文翻译：

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线粒体蛋白导入作为质量控制传感器

线粒体是涉及与细胞代谢和稳态相关的各种功能的细胞器。虽然线粒体包含自己的基因组，但它们的核对应物编码大多数不同的线粒体蛋白。这些在胞质溶胶中作为前体合成并且必须被递送到线粒体中。因此，这些细胞器具有用于从细胞质中导入前体蛋白质的精密机器。存在于线粒体膜和水室中的蛋白质输入机制在蛋白质前识别、易位和穿过或进入其中的分类方面表现出很大的可变性。线粒体蛋白质输入机制还与呼吸链的其他蛋白质复合物或参与维持膜结构的蛋白质复合物瞬时相互作用。因此，线粒体蛋白质易位是维持蛋白质生物发生、生物能量学、膜动力学和细胞器质量控制的调节网络不可或缺的一部分。与线粒体输入缺陷相关的各种压力条件和疾病会导致细胞转录组学和蛋白质组学谱的变化。线粒体蛋白输入功能障碍也会导致前体蛋白过度积累及其在细胞质中的聚集。可以激活多种途径来缓冲这些有害后果。在这里，我们全面介绍了进口机械及其在细胞质量控制中的作用，以应对有缺陷的线粒体进口。我们还讨论了神经退行性疾病和癌症中线粒体蛋白输入功能障碍的病理后果。