Decision letter: Mechanism of cargo-directed Atg8 conjugation during selective autophagy

A living cell must remove unhealthy or excess material from its interior in order to remain healthy and operational. Cells pack this waste into membrane-bound compartments named autophagosomes in a process called autophagy. So-called autophagy proteins make sure that only the unwanted material is eliminated. However, it was not completely clear how these proteins achieve this. What was known was that proteins called cargo receptors recognize and bind to specific waste materials. At the same time, so-called autophagy enzymes tag the membranes of the autophagosome with a protein known as Atg8, so that cargo receptor molecules can bind this membrane. Now, Fracchiolla, Sawa-Makarska et al. report that, in yeast, an autophagy enzyme links these two events by binding to the cargo receptor and promoting the tagging of the autophagosome’s membrane at the same place. The enzyme in question is a complex made from three autophagy proteins (called Atg12, Atg5 and Atg16), and its activity ensures that the membrane is tagged only next to those materials that need to be disposed of. Although it is now clearer how a cell’s waste ends up in the autophagosome, it is still puzzling how this process is regulated and how the other autophagy-related components contribute to this highly coordinated process. In particular, an important next step will be to find out what is the source of membrane that gives rise to the autophagosome.