Figure 7

Schematic model demonstrating the elevation of miR-34a impairs autophagic flux through ATG9A. ATG9A, the only multipass transmembrane ATG protein, is required for the expansion of autophagic membranes. Under normal condition, the initiation of autophagy includes the formation of the phagophore, membrane closure to encapsulate contents in the autophagosome. Completion of the autophagosome is followed by fusion with lysosomes and degradation of the contents. We favor the hypothesis that in the case of miR-34a overexpression, miR-34a inhibition of ATG9A impairs autophagosome biogenesis leading to phagophore accumulation. Therefore, the formation of autophagosome is inhibited and the autophagic flux is limited. LC3-II is specifically associated with phagophore and autophagosome membranes serving as a widely used marker to monitor autophagy levels. Another autophagy marker is p62, which is efficiently degraded upon autophagy induction and serves as an index of autophagic degradation