Li Hongyu, Gao Lixiong, Du Jinlin, Ma Tianju, Li Wen, Ye Zi, Li Zhaohui
Medical School of Chinese PLA, Beijing, China.
Senior Department of Ophthalmology, the Third Medical Center of PLA General Hospital, Beijing, China.
Mol Biol Rep. 2023 May;50(5):4551-4564. doi: 10.1007/s11033-023-08323-6. Epub 2023 Mar 6.
The thorough degeneration of organelles in the core of the lens is certainly a hallmark event during the lens development. Organelles degradation in the terminal differentiation process of lens fiber cells to form an organelle-free zone is critical for lens maturation and transparency. Several mechanisms have been proposed to expand our understanding of lens organelles degradation, including apoptotic pathways, the participation of ribozyme, proteolytic enzyme and phospholipase A and acyltransferase, and the newly discovered roles for autophagy. Autophagy is a lysosome-dependent degradation reaction during which the "useless" cellular components are degraded and recycled. These cellular components, such as incorrectly folded proteins, damaged organelles and other macromolecules, are first engulfed by the autophagosome before being further delivered to lysosomes for degradation. Although autophagy has been recognized involving in organelle degradation of the lens, the detailed functions remain to be discovered. Recent advances have revealed that autophagy not only plays a vital role in the intracellular quality control of the lens but is also involved in the degradation of nonnuclear organelles in the process of lens fiber cell differentiation. Herein, we first review the potential mechanisms of organelle-free zone formation, then discuss the roles of autophagy in intracellular quality control and cataract formation, and finally substantially summarize the potential involvement of autophagy in the development of organelle-free zone formation.
晶状体核心细胞器的彻底退化无疑是晶状体发育过程中的一个标志性事件。晶状体纤维细胞在终末分化过程中进行细胞器降解以形成无细胞器区,这对晶状体的成熟和透明度至关重要。人们提出了几种机制来加深我们对晶状体细胞器降解的理解,包括凋亡途径、核酶、蛋白水解酶、磷脂酶A和酰基转移酶的参与,以及新发现的自噬作用。自噬是一种依赖溶酶体的降解反应,在此过程中,“无用的”细胞成分被降解并循环利用。这些细胞成分,如错误折叠的蛋白质、受损的细胞器和其他大分子,首先被自噬体吞噬,然后被进一步输送到溶酶体进行降解。尽管自噬已被认为参与晶状体的细胞器降解,但其详细功能仍有待发现。最近的研究进展表明,自噬不仅在晶状体的细胞内质量控制中起着至关重要的作用,而且还参与晶状体纤维细胞分化过程中非核细胞器的降解。在此,我们首先回顾无细胞器区形成的潜在机制,然后讨论自噬在细胞内质量控制和白内障形成中的作用,最后全面总结自噬在无细胞器区形成发展中的潜在参与情况。