Glial UDP-glycosyltransferase Ugt35b regulates longevity by maintaining lipid homeostasis in Drosophila
Lipid droplets (LDs) are dynamic organelles essential for lipid storage and organismal survival. Studies have highlighted the importance of glial function in brain LD formation during aging, however, the genes and mechanisms involved remain elusive. Here, we found that Ugt35b, a member of the UDP-glycosyltransferases that catalyze the transfer of glycosyl groups to acceptors, is highly expressed in glia and crucial for Drosophila lifespan. By integrating multi-omics data, we demonstrated that glial Ugt35b plays key roles in regulating glycerolipid and glycerophospholipid metabolism in the brain. Notably, we found that Ugt35b and Lsd-2 are co-expressed in glia and confirmed their protein interaction in vivo. Knockdown of Ugt35b significantly reduces LD formation by downregulating Lsd-2 expression, while overexpression of Lsd-2 partially rescues the shortened lifespan in glial Ugt35b RNAi flies. Our findings reveal the crucial role of glial Ugt35b in regulating LD formation to maintain brain lipid homeostasis and support Drosophila lifespan. Overall design: To elucidate potential molecular alterations contributing to reduced lifespan, we conducted bulk RNA-seq analysis on the heads of flies pan-glial (Repo-GS) expressing Ugt35b RNAi, subjected to either EtOH or RU486 treatment at day 10.