Abstract:
Proteins are known to perform an astonishing array of functions thanks to their ability to cooperate and modulate each other\'s properties. Inside cells, proteins can assemble into large multi-subunit complexes to carry out complex cellular functions. The correct assembly and maintenance of the functional state of macromolecular protein complexes is crucial for human health. Failure to do so leads to loss of function and potential accumulation of harmful materials, which is associated with a variety of human diseases such as neurodegeneration and cancer. Autophagy engulfs cytosolic material in autophagosomes, and therefore is best suited to eliminate intact macromolecular complexes without disassembling them, which could interfere with de novo assembly. In this review, we discuss the role of autophagy in the selective degradation of macromolecular complexes. We highlight the current state of knowledge for different macromolecular complexes and their selective autophagic degradation. We emphasize the gaps in our understanding of what it takes for these large macromolecular complexes to be degraded and point to future work that may shed light on the regulation of the selective degradation of macromolecular complexes by autophagy.
摘要:
众所周知,蛋白质具有惊人的功能阵列,这要归功于它们相互协作和调节彼此特性的能力。细胞内部,蛋白质可以组装成大型多亚基复合物来执行复杂的细胞功能。正确组装和维持大分子蛋白质复合物的功能状态对人类健康至关重要。否则会导致功能丧失和有害物质的潜在积累,它与多种人类疾病如神经变性和癌症有关。自噬吞噬自噬体中的胞浆物质,因此最适合消除完整的大分子复合物而不分解它们,这可能会干扰从头组装。在这次审查中,我们讨论了自噬在大分子复合物选择性降解中的作用。我们重点介绍了不同大分子复合物及其选择性自噬降解的最新知识。我们强调了我们对这些大分子复合物降解所需的理解的空白,并指出了未来的工作,这些工作可能会阐明通过自噬调节大分子复合物的选择性降解。