Zonda: a novel gene involved in autophagy and growth control

MARIANA MELANI; NURIA M. ROMERO; JULIETA MARIA ACEVEDO; JOEL PEREZ PERRI; PABLO WAPPNER

Santiago de Chile

Workshop; Visualization and manipulation of signal and forces in developing tissues; 2014

The autophagic degradative pathway depends on the novo formation of a membranous organelle, the phagophore. The mechanistic aspects of how this pathway is controlled, and what regulates the formation of this organelle remains mysterious. We describe the function of a novel Drosophila gene, zonda, as an important regulator of autophagy. We found that Zonda is absolutely required for autophagy. Zonda-depleted fat body cells from Drosophila larvae fail to induce autophagy upon starvation, as concluded after analyzing several autophagy markers including: ATG8 nucleation, lysotracker incorporation, Lamp-1 distribution and Ref2(P) accumulation. Starvation-induced nucleation of Zonda depends on ATG1 but not on the PI3K VPS34. Moreover, Zonda is required for starvation-induced VPS34 activation, as assayed by analyzing the distribution of FYVE-GFP, a reporter of PI3P accumulation. Overexpression of Zda can induce autophagy independently of the nutritional state. Finally, Zonda subcelullar distribution is sensitive to nutrients: whereas in well-fed larvae it presents a vesiculo-reticulated distribution, upon starvation, Zonda concentrates in discrete foci that co-localize with ATG-8 Altogether, these results indicate that Zonda is a novel autophagy gene that might act at relatively early steps of the autophagic cascade.