Spargel/ PGC-1 is the new terminal effector in the Insulin-Tor Signaling pathway. Subhas Mukherjee, Atanu Duttaroy. Biology, Howard University, Washington, DC.
Insulin and Tor signaling pathways converge to maintain growth so a proportionate body form is attained. Spargel is the Drosophila homolog of PGC-1, which is an omnipotent transcriptional co-activator in mammals. Spargel/PGC-1 is recognized for their role in energy metabolism through mitochondrial biogenesis. Some studies have indicated that spargel/PGC-1 is possibly involved in insulin-TOR signaling, although a comprehensive analysis is still lacking. Using genetic epistasis analysis, we demonstrated that spargel action is necessary for TOR and S6K to regulate cell size and cell growth in a cell autonomous manner, as well as the tissue-restricted phenotypes of TOR and S6K mutants are also rescued by spargel overexpression. We show that spargel overexpression sets back the mitochondrial numbers and increases ATP production, which helps the cells and tissue to attain normal size. With regard to its interaction with FoxO, an important player in the insulin-signaling pathway, excess spargel, can ameliorate the FoxO overexpression defects although at a limited capacity. We therefore conclude that spargel functions as a terminal effector in the insulin-TOR pathway and should be incorporated as a new member of this growth-signaling pathway.