RT Journal Article SR Electronic T1 An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 323956 DO 10.1101/323956 A1 Sider Penkov A1 Cihan Erkut A1 Jana Oertel A1 Roberta Galli A1 Daniela Vorkel A1 Jean-Marc Verbavatz A1 Edmund Koch A1 Karim Fahmy A1 Teymuras V. Kurzchalia YR 2018 UL http://biorxiv.org/content/early/2018/05/16/323956.abstract AB The ability of organisms to adapt to environmental changes and regulate the balance between growth and quiescence depend on global transitions in metabolic state. Under harsh environmental conditions, C. elegans enters diapause and forms a specialized dauer larva. This larva has a specific morphology and its metabolism switches from the tricarboxylic acid (TCA) cycle to gluconeogenesis. Here, we show that these changes involve concerted activity of several regulatory pathways. Whereas the insulin pathway maintains low energy expenditure through the FoxO transcription factor DAF-16, dauer morphogenesis is controlled by the steroid hormone receptor DAF-12. We show that downstream or in parallel to DAF-16 operates the AMPK α-subunit AAK-2. AAK-2 and DAF-12 separately promote a switch from TCA cycle to gluconeogenesis, serving as metabolic “turnouts to a slow lane”. When both are suppressed, the TCA cycle is active and the developmental arrest is abolished. Thus, a global metabolic switch governs the transition between growth and quiescence.