Background

Perturbations in organellar health can lead to an accumulation of unwanted and/or damaged organelles that are toxic to the cell and which can contribute to the onset of neurodegenerative diseases such as Parkinson's disease. Mitochondrial health is particularly critical given the indispensable role the organelle has not only in adenosine triphosphate production but also other metabolic processes. Byproducts of oxidative respiration, such as reactive oxygen species, however, can negatively impact mitochondrial fitness. Consequently, selective degradation of damaged mitochondria, which occurs via a specific autophagic process termed mitophagy, is essential for normal cell maintenance.

Scope of review

Recent accumulating evidence has shown that autophagy adaptors (also referred to as autophagy receptors) play critical roles in connecting ubiquitinated mitochondria with the autophagic machinery of the autophagy-lysosome pathway that is required for degradation. In this review, we focus on our current understanding of the autophagy adaptor mechanisms underlying PINK1/Parkin-driven mitophagy.

Major conclusions

Although autophagy adaptors are canonically defined as proteins that possess ubiquitin-binding domains and ATG8s-binding motifs, the recent identification of novel binding partners has contributed to the development of a more sophisticated model for how autophagy adaptors contribute to the molecular hub that organizes autophagic cargo-degradation.

General significance

Although mitophagy is recognized as one of the selective autophagy pathways that removes dysfunctional mitochondria, a more nuanced understanding of the interactions connecting autophagy adaptors and their associated proteins is needed to gain deeper insights into the fundamental biological processes underlying human diseases, including neurodegenerative disorders. This review is part of a Special Issue entitled Mitophagy.

中文翻译：

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自噬接头对泛素驱动线粒体自噬的分子功能

背景

细胞器健康的扰动会导致不需要的和/或受损的细胞器积累，这些细胞器对细胞有毒，并可能导致神经退行性疾病（如帕金森病）的发作。鉴于细胞器不仅在三磷酸腺苷生产中而且在其他代谢过程中都起着不可或缺的作用，因此线粒体健康尤为重要。然而，氧化呼吸的副产物，如活性氧，会对线粒体健康产生负面影响。因此，通过称为线粒体自噬的特定自噬过程发生的受损线粒体的选择性降解对于正常细胞维持至关重要。

审查范围

最近积累的证据表明，自噬接头（也称为自噬受体）在连接泛素化线粒体与降解所需的自噬-溶酶体途径的自噬机制方面发挥着关键作用。在这篇综述中，我们专注于我们目前对 PINK1/Parkin 驱动的线粒体自噬背后的自噬适配器机制的理解。

主要结论

尽管自噬接头被规范地定义为具有泛素结合域和 ATG8s 结合基序的蛋白质，但最近发现的新型结合伙伴有助于开发更复杂的模型，以了解自噬接头如何促进组织自噬货物的分子中心-降解。

一般意义

尽管线粒体自噬被认为是去除功能失调线粒体的选择性自噬途径之一，但需要更细致地了解连接自噬接头及其相关蛋白质的相互作用，以更深入地了解人类疾病（包括神经退行性疾病）的基本生物学过程。这篇评论是题为 Mitophagy 的特刊的一部分。