Under starvation, animals are expected to stop lipogenesis and initiate lipolysis to mobilize energy stored in the form of neutral lipids. Diacylglycerol acyltransferase (DGAT2) plays an important role in lipogenesis. It synthesizes triacylglycerol by catalyzing the addition of long chain fatty acyl-CoA to diacylglycerol. Understanding of DGAT2 regulation can reveal the molecular mechanism that underlies the transition from fat synthesis to fat utilization. In C. elegans, the DGAT2 ortholog is preferentially degraded in starved animals in comparison to a LD resident structural protein. Preliminary evidence suggested that DGAT2 was degraded through the ER-associated degradation (ERAD) pathway. The ERAD pathway is composed of multiple ubiquitin E3 ligases and their associated proteins. Ho...[ Read more ]

Under starvation, animals are expected to stop lipogenesis and initiate lipolysis to mobilize energy stored in the form of neutral lipids. Diacylglycerol acyltransferase (DGAT2) plays an important role in lipogenesis. It synthesizes triacylglycerol by catalyzing the addition of long chain fatty acyl-CoA to diacylglycerol. Understanding of DGAT2 regulation can reveal the molecular mechanism that underlies the transition from fat synthesis to fat utilization. In C. elegans, the DGAT2 ortholog is preferentially degraded in starved animals in comparison to a LD resident structural protein. Preliminary evidence suggested that DGAT2 was degraded through the ER-associated degradation (ERAD) pathway. The ERAD pathway is composed of multiple ubiquitin E3 ligases and their associated proteins. However, the specific ERAD components that are required for degrading DGAT2 under starvation have been ill-defined. Here, I report the components that are required for the degradation of DGAT2 ortholog in starved worms by using genetic, biochemical as well as live-cell imaging approaches.