Wang Liming, Klionsky Daniel J, Shen Han-Ming
School of Biomedical Sciences, Hunan University, Changsha, China.
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Nat Rev Mol Cell Biol. 2023 Mar;24(3):186-203. doi: 10.1038/s41580-022-00529-z. Epub 2022 Sep 12.
'Autophagy' refers to an evolutionarily conserved process through which cellular contents, such as damaged organelles and protein aggregates, are delivered to lysosomes for degradation. Different forms of autophagy have been described on the basis of the nature of the cargoes and the means used to deliver them to lysosomes. At present, the prevailing categories of autophagy in mammalian cells are macroautophagy, microautophagy and chaperone-mediated autophagy. The molecular mechanisms and biological functions of macroautophagy and chaperone-mediated autophagy have been extensively studied, but microautophagy has received much less attention. In recent years, there has been a growth in research on microautophagy, first in yeast and then in mammalian cells. Here we review this form of autophagy, focusing on selective forms of microautophagy. We also discuss the upstream regulatory mechanisms, the crosstalk between macroautophagy and microautophagy, and the functional implications of microautophagy in diseases such as cancer and neurodegenerative disorders in humans. Future research into microautophagy will provide opportunities to develop novel interventional strategies for autophagy- and lysosome-related diseases.
“自噬”指的是一个进化上保守的过程,通过该过程,细胞内容物,如受损的细胞器和蛋白质聚集体,被输送到溶酶体进行降解。根据货物的性质以及将它们输送到溶酶体的方式,已描述了不同形式的自噬。目前,哺乳动物细胞中自噬的主要类别是巨自噬、微自噬和伴侣介导的自噬。巨自噬和伴侣介导的自噬的分子机制和生物学功能已得到广泛研究,但微自噬受到的关注要少得多。近年来,对微自噬的研究不断增加,首先是在酵母中,然后是在哺乳动物细胞中。在此,我们综述这种自噬形式,重点关注微自噬的选择性形式。我们还讨论了上游调控机制、巨自噬和微自噬之间的相互作用,以及微自噬在人类癌症和神经退行性疾病等疾病中的功能意义。未来对微自噬的研究将为开发针对自噬和溶酶体相关疾病的新型干预策略提供机会。