An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase.
An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase.
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DOI：
10.15252/embr.202152669
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发表时间：
2022-02-03
期刊：
影响因子：
7.7
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
Zhao X;Wang W;Yao Y;Li X;Huang X;Wang Y;Ding M;Huang X
脂滴的大小在体内变化很大，由内在和外在因素决定。从果蝇中的RNAi筛选中，我们发现敲低COP 9信号体（CSN）的亚基会导致高脂肪条件下的脂滴增大，但不是正常条件下的脂滴。我们确定CG 2064，视黄醇脱氢酶（RDH）同源物，作为CSN调节脂滴大小的蛋白酶体降解靶点。RDH/CG 2064与脂滴驻留蛋白Plin 2相互作用，并且RDH/CG 2064-Plin 2轴起到降低Bmm/ATGL脂肪酶的总体水平和脂滴定位的作用。这个轴对于幼虫在长期饥饿下的存活是重要的。因此，我们发现RDH-Plin 2轴调节脂滴大小。RNAi筛选鉴定了COP 9信号体（CSN）的亚基作为高脂肪条件下脂滴形成的负调节剂。CSN诱导RDH的蛋白酶体降解，从而促进Plin 2定位于核周脂滴。
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. 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.