Zonda is a novel early component of the autophagy pathway in Drosophila

MARIANA MELANI

Conferencia; Buenos Aires Research Conference on Autophagy; 2017

The first distinguishable autophagy-specific membranous structure, the omegasome, forms when the VPS34 autophagy nucleation complex (VPS34, BECN1/ATG6, ATG14 and VPS15) mediates local deposition of phospatidylinositol-3-phospate (PI3P) in a specific domain of the ER. The molecules and mechanisms that mediate targeting of this complex and localized deposition of PI3P remain however poorly defined. We found that Zonda is required for Vps34-mediated PI3P deposition. Zonda displays an even distribution under basal conditions and soon after starvation nucleates in endoplasmic reticulum-associated foci that colocalize with omegasome markers. Starvation-induced Zonda nucleation depends on Atg1, Atg13 and Atg17 but does not require Vps34, Vps15, Atg6 or Atg14. Zonda interacts physically with ATG1 through its kinase domain, as well as with ATG6 and Vps34. Moreover, Zonda overexpression is sufficient to trigger a bonafide autophagic response as evaluated by transmission electron microscopy as well as several autophagic markers. We propose that Zonda is an early component of the autophagy cascade necessary for Vps34-dependent PI3P deposition and omegasome formation.