Organelle degradation in the lens by PLAAT phospholipases

Hideaki Morishita (), Tomoya Eguchi, Satoshi Tsukamoto, Yuriko Sakamaki, Satoru Takahashi, Chieko Saito, Ikuko Koyama-Honda and Noboru Mizushima ()
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Hideaki Morishita: The University of Tokyo
Tomoya Eguchi: The University of Tokyo
Satoshi Tsukamoto: National Institutes for Quantum and Radiological Science and Technology
Yuriko Sakamaki: Tokyo Medical and Dental University
Satoru Takahashi: The University of Tokyo
Chieko Saito: The University of Tokyo
Ikuko Koyama-Honda: The University of Tokyo
Noboru Mizushima: The University of Tokyo

Nature, 2021, vol. 592, issue 7855, 634-638

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03439-w

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