PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle
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 rege...
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Elsevier
2023-02-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472300102X |
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author | Miwa Hara Wenjing Wu Volha V. Malechka Yusuke Takahashi Jian-Xing Ma Gennadiy Moiseyev |
author_facet | Miwa Hara Wenjing Wu Volha V. Malechka Yusuke Takahashi Jian-Xing Ma Gennadiy Moiseyev |
author_sort | Miwa Hara |
collection | DOAJ |
description | 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. |
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id | doaj.art-f05f525653e6473e982fa23b0ca5e2a2 |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-04-10T16:07:39Z |
publishDate | 2023-02-01 |
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series | Cell Reports |
spelling | doaj.art-f05f525653e6473e982fa23b0ca5e2a22023-02-10T04:21:50ZengElsevierCell Reports2211-12472023-02-01422112091PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycleMiwa Hara0Wenjing Wu1Volha V. Malechka2Yusuke Takahashi3Jian-Xing Ma4Gennadiy Moiseyev5Department 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, USADepartment 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, USADepartment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment 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, USADepartment 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, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S221112472300102XCP: Metabolism |
spellingShingle | Miwa Hara Wenjing Wu Volha V. Malechka Yusuke Takahashi Jian-Xing Ma Gennadiy Moiseyev PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle Cell Reports CP: Metabolism |
title | PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle |
title_full | PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle |
title_fullStr | PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle |
title_full_unstemmed | PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle |
title_short | PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle |
title_sort | pnpla2 mobilizes retinyl esters from retinosomes and promotes the generation of 11 cis retinal in the visual cycle |
topic | CP: Metabolism |
url | http://www.sciencedirect.com/science/article/pii/S221112472300102X |
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