2. Academic Validation
  3. PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle

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

  • Cell Rep. 2023 Feb 8;42(2):112091. doi: 10.1016/j.celrep.2023.112091.
Miwa Hara 1,  Wenjing Wu 1,  Volha V Malechka 2,  Yusuke Takahashi 1,  Jian-Xing Ma 1,  Gennadiy Moiseyev 3
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • 3 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. Electronic address: gmoiseye@wakehealth.edu.
PMID: 36763501 DOI: 10.1016/j.celrep.2023.112091
Abstract

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.

Keywords

11-cis-retinol; CP: Metabolism; PNPLA2; lipid droplets; retinosomes; retinyl ester hydrolase.

Figures
Products