As a central hub for cellular metabolism and intracellular signalling, the mitochondrion is a pivotal organelle, dysfunction of which has been linked to several human diseases including neurodegenerative disorders, and in particular Parkinson's disease. An inherent challenge that mitochondria face is the continuous exposure to diverse stresses which increase their likelihood of dysregulation. In response, eukaryotic cells have evolved sophisticated quality control mechanisms to monitor, identify, repair and/or eliminate abnormal or misfolded proteins within the mitochondrion and/or the dysfunctional mitochondrion itself. Chaperones identify unstable or otherwise abnormal conformations in mitochondrial proteins and can promote their refolding to recover their correct conformation and stability. However, if repair is not possible, the abnormal protein is selectively degraded to prevent potentially damaging interactions with other proteins or its oligomerization into toxic multimeric complexes. The autophagic-lysosomal system and the ubiquitin-proteasome system mediate the selective and targeted degradation of such abnormal or misfolded protein species. Mitophagy (a specific kind of autophagy) mediates the selective elimination of dysfunctional mitochondria, in order to prevent the deleterious effects the dysfunctional organelles within the cell. Despite our increasing understanding of the molecular responses toward dysfunctional mitochondria, many key aspects remain relatively poorly understood. Herein, we review the emerging mechanisms of mitochondrial quality control including quality control strategies coupled to mitochondrial import mechanisms. In addition, we review the molecular mechanisms regulating mitophagy with an emphasis on the regulation of PINK1/PARKIN-mediated mitophagy in cellular physiology and in the context of Parkinson's disease cell biology.

中文翻译：

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健康和帕金森病中的线粒体质量控制

作为细胞代谢和细胞内信号传导的中心枢纽，线粒体是一个关键的细胞器，其功能障碍与多种人类疾病有关，包括神经退行性疾病，特别是帕金森病。线粒体面临的一个固有挑战是持续暴露于各种压力，这增加了它们失调的可能性。作为回应，真核细胞已经进化出复杂的质量控制机制来监测、识别、修复和/或消除线粒体和/或功能失调的线粒体本身内的异常或错误折叠的蛋白质。分子伴侣识别线粒体蛋白中不稳定或异常的构象，并可以促进它们的重新折叠以恢复其正确的构象和稳定性。但是，如果无法修复，异常蛋白质被选择性降解以防止与其他蛋白质的潜在破坏性相互作用或其寡聚化成有毒的多聚体复合物。自噬-溶酶体系统和泛素-蛋白酶体系统介导这种异常或错误折叠的蛋白质种类的选择性和靶向降解。线粒体自噬（一种特殊的自噬​​）介导选择性消除功能失调的线粒体，以防止细胞内功能失调的细胞器产生有害影响。尽管我们越来越了解对功能失调的线粒体的分子反应，但许多关键方面仍然知之甚少。在此，我们回顾了线粒体质量控制的新兴机制，包括与线粒体输入机制相结合的质量控制策略。此外，