RRC ID 70448
Author Morishita H, Eguchi T, Tsukamoto S, Sakamaki Y, Takahashi S, Saito C, Koyama-Honda I, Mizushima N.
Title Organelle degradation in the lens by PLAAT phospholipases.
Journal Nature
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 mice4-6-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.
Volume 592(7855)
Pages 634-638
Published 2021-4-1
DOI 10.1038/s41586-021-03439-w
PII 10.1038/s41586-021-03439-w
PMID 33854238
MeSH Acyltransferases / metabolism Animals Cataract / metabolism Cell Line Female Heat Shock Transcription Factors / metabolism Intracellular Membranes / metabolism Intracellular Membranes / pathology Lens, Crystalline / cytology* Lens, Crystalline / enzymology* Male Mice Mice, Inbred C57BL Organelles / metabolism* Phospholipases A / metabolism* Phospholipases A2, Calcium-Independent / metabolism* Protein Transport Zebrafish / metabolism Zebrafish Proteins / metabolism*
IF 42.779
Resource
Zebrafish RIKEN WT