An RDH‐Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase. (8th February 2022)

• Record Type: Journal Article
• Authors: Zhao, Xuefan; Wang, Wei; Yao, Yan; Li, Xia; Huang, Xiahe; Wang, Yingchun; Ding, Mei; Huang, Xun
• Is Part Of: EMBO reports. Volume 23:Number 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-08
• Subjects: ATGL -- large lipid droplet -- RDH/Plin2; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202152669
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high‐fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet‐resident protein Plin2 and the RDH/CG2064‐Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH‐Plin2 axis modulates lipid droplet size. SYNOPSIS: An RNAi screen identifies subunits of COP9 signalosome (CSN) as negative regulators of lipid droplet formation under high fat conditions. CSN induces proteasomal degradation of RDH, which promotes Plin2 localization to the perinuclear lipid droplets. CSN deficiency causes formation of large lipid droplets under high‐fat conditions. CSN regulates lipid droplet size by proteasomal degradation of RDH/CG2064. RDH/CG2064 interacts with Plin2 and promotes its localization to the perinuclear lipid droplets. The RDH‐Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. Abstract : An RNAi screen identifies subunits of COP9 signalosome (CSN) as negative regulators of lipid droplet formation under high fat conditions. CSN induces proteasomal degradation of RDH, which promotes Plin2 localization to the perinuclear lipid droplets.