PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle

Miwa Hara; Wenjing Wu; Volha V. Malechka; Yusuke Takahashi; Jian-Xing Ma; Gennadiy Moiseyev

Cell Reports (Feb 2023)

PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle

Miwa Hara,
Wenjing Wu,
Volha V. Malechka,
Yusuke Takahashi,
Jian-Xing Ma,
Gennadiy Moiseyev

Affiliations

Miwa Hara: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Wenjing Wu: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Volha V. Malechka: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Yusuke Takahashi: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Jian-Xing Ma: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA
Gennadiy Moiseyev: Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston Salem, NC 27157, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 2
p. 112091

Abstract

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Summary: Retinosomes are intracellular lipid bodies found in the retinal pigment epithelium (RPE). They contain retinyl esters (REs) and are thought to be involved in visual chromophore regeneration during dark adaptation and in case of chromophore depletion. However, key enzymes in chromophore regeneration, retinoid isomerase (RPE65), and lecithin:retinol acyltransferase (LRAT) are located in the endoplasmic reticulum (ER). The mechanism and the enzyme responsible for mobilizing REs from retinosomes remained unknown. Our study demonstrates that patatin-like phospholipase domain containing 2 (PNPLA2) mobilizes all-trans-REs from retinosomes. The absence of PNPLA2 in mouse eyes leads to a significant accumulation of lipid droplets in RPE cells, declined electroretinography (ERG) response, and delayed dark adaptation compared with those of WT control mouse. Our work suggests a function of PNPLA2 as an RE hydrolase in the RPE, mobilizing REs from lipid bodies and functioning as an essential component of the visual cycle.

CP: Metabolism

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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