Emerging roles of E3 ubiquitin ligases in autophagy

• Sequential conjugation of ATGs mimics the ubiquitin conjugation process.
• Most ubiquitin ligases involved in autophagy act on upstream regulatory components.
• RNF5, TRAF6, and Nedd4 exemplify ubiquitin ligases that affect the key autophagy components ATG4B and Beclin 1.

Autophagy is an evolutionarily conserved intracellular catabolic process that delivers cytoplasmic components to lysosomes for degradation and recycling. Although originally considered to be a non-selective pathway, it is now recognized that autophagy is involved in selective processes, including the turnover of organelles, removal of protein aggregates, and elimination of intracellular pathogens. This specificity implies that cargo recognition and processing by the autophagy machinery are tightly regulated processes. In support of this, various forms of post-translational modification have been implicated in the regulation of autophagy, one of which is the ubiquitin–proteasome system. Here we review current understanding of the role of ubiquitylation in the control of autophagy.