Gcn5 and mTORC1 mediated regulation of autophagy controls Drosophila blood cell homeostasis

Abstract Blood progenitors are regulated by a variety of systemic and nutritional cues from their environment. In the Drosophila lymph gland (LG), the Posterior Signalling Center (PSC) acts as a stem cell niche striking a balance between progenitors and differentiated blood cells. Autophagy is a vital cellular process that maintains homeostasis by removing unnecessary or dysfunctional cell components through autophagic degradation and recycling. Here, using genetic perturbation analysis, we show that autophagy plays a critical role in regulating LG blood cell homeostasis. General control non-derepressible 5 (Gcn5), a histone acetyltransferase is expressed in the primary LG lobe and modulation of Gcn5 levels perturbs LG homeostasis. Our results show that hemocyte-specific Gcn5 modulation controls autophagic flux in the hemocytes. Furthermore, we show that modulation of mTORC1 activity can perturb hematopoiesis. Our results indicate that organismal Gcn5 levels respond to dietary shifts and are modulated by mTORC1 signaling. Chemical intervention shows that mTORC1 over-rides the effect exerted by Gcn5 in regulating LG hematopoiesis. Taken together, our findings demonstrate that Gcn5 and mTORC1 regulates autophagy to maintain blood cell homeostasis in Drosophila .