小柯机器人

日本东京大学Noboru Mizushima、Hideaki Morishita等研究人员合作发现，PLAAT磷脂酶降解晶状体中的细胞器。该项研究成果于2021年4月14日在线发表在《自然》杂志上。

研究人员发现，小鼠中PLAAT（磷脂酶A/酰基转移酶，也称为HRASLS）家族中的磷脂酶，在斑马鱼中为Plaat1（也称为Hrasls），在小鼠中为PLAAT3（也称为HRASLS3、PLA2G16、H-rev107或AdPLA），对于线粒体、内质网和溶酶体等晶状细胞器的降解至关重要。Plaat1和PLAAT3在细胞器降解之前立即从胞质溶胶迁移至各种细胞器，其过程需要它们的C端跨膜结构域。

Plaat1向细胞器的转运取决于纤维细胞的分化和细胞器膜的损伤，两者均由Hsf4介导。Plaat1或PLAAT3易位至膜后，磷脂酶诱导广泛的细胞器破裂，然后完全降解。PLAAT家族磷脂酶降解细胞器对于实现晶状体的最佳透明度和折射功能至关重要。这些发现扩大了人们对细胞内细胞器降解的理解，并为脊椎动物获得透明晶状体的机理提供了见解。

据介绍，脊椎动物的眼睛晶状体由纤维细胞组成，其中所有膜结合的细胞器在终末分化过程中都会降解，形成无细胞器的区域。尽管以前已证明这个过程不依赖于巨自噬，但仍是导致大规模细胞器降解的基础机制尚不清楚。

附：英文原文

Title: Organelle degradation in the lens by PLAAT phospholipases

Author: Hideaki Morishita, Tomoya Eguchi, Satoshi Tsukamoto, Yuriko Sakamaki, Satoru Takahashi, Chieko Saito, Ikuko Koyama-Honda, Noboru Mizushima

Issue&Volume: 2021-04-14

Abstract: The eye lens of vertebrates is composed of fibre cells in which all membrane-bound organelles undergo degradation during terminal differentiation to form an organelle-free zone1. The mechanism that underlies this large-scale organelle degradation remains largely unknown, although it has previously been shown to be independent of macroautophagy2,3. Here we report that phospholipases in the PLAAT (phospholipase A/acyltransferase, also known as HRASLS) family—Plaat1 (also known as Hrasls) in zebrafish and PLAAT3 (also known as HRASLS3, PLA2G16, H-rev107 or AdPLA) in mice4,5,6—are essential for the degradation of lens organelles such as mitochondria, the endoplasmic reticulum and lysosomes. Plaat1 and PLAAT3 translocate from the cytosol to various organelles immediately before organelle degradation, in a process that requires their C-terminal transmembrane domain. The translocation of Plaat1 to organelles depends on the differentiation of fibre cells and damage to organelle membranes, both of which are mediated by Hsf4. After the translocation of Plaat1 or PLAAT3 to membranes, the phospholipase induces extensive organelle rupture that is followed by complete degradation. Organelle degradation by PLAAT-family phospholipases is essential for achieving an optimal transparency and refractive function of the lens. These findings expand our understanding of intracellular organelle degradation and provide insights into the mechanism by which vertebrates acquired transparent lenses.

DOI: 10.1038/s41586-021-03439-w

Source: https://www.nature.com/articles/s41586-021-03439-w

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