Autophagosome biogenesis

The mechanism of autophagosome biogenesis is still elusive. Our knowledge concerning the order of incorporation of the different factors into sites of autophagosome formation, as well as on the functional complexes involved in this process, has increased substantially in recent years. However, the exact details concerning the way in which all of these factors act in concert are still missing. The reconstitution of such a step in the test tube will clearly be very challenging, but if successful it will provide invaluable information on this process.
There are several open questions remaining in this field including: How do Atg9-containing vesicles contribute to autophagosome biogenesis? How are the SNARE molecules needed for fusion of the autophagosome with the lysosome incorporated into the outer autophagosomal membrane? How are the inner and outer membranes of the phagophore sorted into two sub-domains? How are the cup-shaped phagophores formed and stabilized? What dictates the final sealing of the autophagosome?