An RDH‐Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase

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.

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets

“…Both PLIN2 protein and ATGL mRNA have previously been detected in nurse cells in mid-oogenesis (Teixeira et al ., 2003; Jambor et al ., 2015). ATGL catalyzes the conversion of triacylglycerol to diacylglycerol and free FA (Gronke et al ., 2005), while PLIN2 is one of the two members of the perilipin family of LD proteins in flies and regulates lipid metabolism by protecting the stored triglycerides from the lipolytic machinery, including ATGL (Gronke et al ., 2003; Beller et al ., 2010; Bi et al ., 2012; Zhao et al ., 2022).…”

“…ATGL is highly expressed in the larval and adult fat body; its absence causes triglyceride overaccumulation in this tissue, while overexpression depletes organismal fat stores (Gronke et al ., 2005). In this context, ATGL and PLIN2 act antagonistically, with ATGL promoting triglyceride breakdown and PLIN2 preventing it (Gronke et al ., 2003; Beller et al ., 2010; Bi et al ., 2012; Zhao et al ., 2022). While our experiments do not address whether a similar antagonism operates in follicles, PLIN2 must affect actin remodeling via a PG-independent mechanism since loss of PLIN2 causes actin defects (Figure 2B) and there is no synergistic effect between PLIN2 and ATGL/Pxt in our dominant genetic interaction tests (Figure 3C, G and I).…”

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets

“…As ATGL catalyzes the conversion of triacylglycerol to diacylglycerol and free FA ( Grönke et al, 2005 ), this pattern raises the possibility that LD triglycerides are broken down during these stages. Using an endogenously tagged ATGL-GFP allele ( Zhao et al, 2022 ), we confirmed that ATGL is expressed in S10B follicles and colocalizes with LDs ( Fig. 2 A-A″).…”

“…Flies used in all other experiments were maintained on molasses/agar/yeast/malt extract/corn flour/soy flour food at room temperature except as noted below. Stocks used were y 1 w 1 [Bloomington Drosophila Stock Center (BDSC), #1495], Oregon R (BDSC, #5), bmm 1 ( Grönke et al, 2003 ), bmm-GFP (BDSC, #94600, ( Zhao et al, 2022 ), pxt f01000 (Harvard Exelixis Collection; Thibault et al, 2004 ), pxt EY03052 (BDSC, #15620), mdy QX25 (BDSC, #5095), Lsd-2 KG00149 (BDSC, #13382), sqh-EYFP-ER (BDSC, #7195; LaJeunesse et al, 2004 ), sqh-EYFP-Golgi (BDSC, #7193; LaJeunesse et al, 2004 ).…”

Perilipin 1 Deficiency Prompts Lipolysis in Lipid Droplets and Aggravates the Pathogenesis of Persistent Immune Activation in <i>Drosophila</i>

“…Fly resources that were used in this study are as follows: w 1118 were used as wild-type controls if there was no additional indication. plin1 38 , Bmm-GFP [ 18 ], UAS-plin1 RNAi , and ppl-GAL4 were kindly gifted from Dr. Xun Huang (Institute of Genetics and Developmental Biology, CAS). UAS-Bmm RNAi (V37880) was obtained from the Vienna Drosophila Resource Center.…”