Gcn5 – mTORC1 – TFEB signalling axis mediated control of autophagy regulates Drosophila blood cell homeostasis

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. Blood progenitors maintain homeostasis by fine tuning intrinsic and extrinsic cues.. Autophagy is one such 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 demonstrate thatGcn5 through its known non-histone acetylation target, TFEB controls autophagic flux in the hemocytes.. Additionally, we show that modulation of mTORC1 activity can perturb hematopoiesis. Our results indicate that Gcn5 acts as a nutrient sensor and modulation of mTORC1 activity regulates Gcn5. Chemical intervention shows that mTORC1 over-rides the effect exerted by Gcn5 in regulating LG hematopoiesis. Taken together, our findings indicate that Gcn5 – mTORC1 – TFEB signaling axis mediated control of autophagy is required for maintaining blood cell homeostasis in Drosophila.