Drosophila STING protein has a role in lipid metabolism

Abstract

Stimulator of interferon genes (STING) plays an important role in innate immunity by controlling type I interferon response against invaded pathogens. In this work we describe a previously unknown role of STING in lipid metabolism in Drosophila. Flies with STING deletion are sensitive to starvation and oxidative stress, have reduced lipid storage and downregulated expression of lipid metabolism genes. We found that Drosophila STING interacts with lipid synthesizing enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). ACC and FASN also interact with each other, indicating that all three proteins may be components of a large multi-enzyme complex. The deletion of Drosophila STING leads to disturbed ACC localization and decreased FASN enzyme activity. Together, our results demonstrate a previously undescribed role of STING in lipid metabolism in Drosophila.

cGAS-like receptor-mediated immunity: the insect perspective

“…What is the relation, if any, between the cGLR-STING pathway and antiviral RNAi? How is this new pathway linked with metabolic regulation in flies [65]? Using the resources of the Drosophila model to answer these questions should provide insight on still mysterious aspects of cGAS-STING biology in mammals.…”

Necrotic debris and STING exert therapeutically relevant effects on tumor cholesterol homeostasis

“…Recently, a direct relationship between STING signaling and cell metabolism has been proposed ( 42 ). STING has been shown to associate with acetyl-CoA carboxylase (ACC) and fatty acid synthase in drosophila, and its deletion was observed to induce major metabolic dysregulation ( 42 ).…”

“…Recently, a direct relationship between STING signaling and cell metabolism has been proposed ( 42 ). STING has been shown to associate with acetyl-CoA carboxylase (ACC) and fatty acid synthase in drosophila, and its deletion was observed to induce major metabolic dysregulation ( 42 ). Our observations indicate that STING activation by its natural ligand cGAMP reduces the cellular cholesterol load by up-regulating genes that encode proteins associated with HDL formation and cholesterol export from the cell.…”

STING1 in Different Organelles: Location Dictates Function

“…Accumulating evidence demonstrates that the subcellular distribution of STING1 is not restricted to an ER-to-Golgi apparatus (Golgi) membranous network. Under different circumstances, the localization on other organelles enables some immune-independent functions of STING1, contributing to autophagy ( 10 ), regulated cell death ( 11 ), ER stress ( 12 ), lipid metabolism ( 13 ), and DNA damage response (DDR) ( 14 ). The participation and crosstalk of these organelles determine the function of STING1 in diseases by controlling its location, binding partners, and signaling recognition.…”