Autophagic bodies in a yeast cell. M. Baba and Y. Ohsumi.

When cells are starving, they can eat almost anything, even their own proteins and organelles. This desperate act — called autophagy — involves the engulfment of cytosol and organelles by a membrane that folds back onto itself, giving rise to an autophagosome.

Screens in the yeast Saccharomyces cerevisiae identified many Apg mutants defective in autophagy, and their characterization is progressing rapidly. About two years ago, Ohsumi and colleagues characterized a ubiquitin-like protein modification necessary for autophagy. Two papers from the same group now describe a second, more unusual, ubiquitin-like modification required for this process.

Apg8 is essential for autophagy in yeast, and starvation increases its transcription. Its weak homology with the ubiquitin-like protein Apg12p suggests that Apg8p might also be a ubiquitin-like protein. Kirisako and colleagues showed that the carboxyl terminus of newly synthesized Apg8p is proteolytically cleaved by the cysteine protease Apg4p. The cleaved form of Apg8p is covalently modified on its terminal glycine and, as a consequence, becomes tightly membrane associated. Ichimura and colleagues determined the nature of this modification and found that it's not a protein, but the lipid phosphatidylethanolamine (PE). The sequence of events leading to the conjugation of Apg8p to PE is reminiscent of ubiquitylation, as Apg8p is first bound to the E1-type enzyme Apg7p, and then to the E2-type enzyme Apg3p, before being finally transferred to PE. The reaction is reversible, and Apg4p can cleave the amide bond.

So what is the function of 'Apg8ylation'? The authors speculate that Apg8 might be part of the fusion machinery involved in the formation of autophagosomes. Or could it be that, much like ubiquitin tags proteins for degradation in the proteasome, Apg8p tags PE-containing membranes for degradation through autophagy?