A selective autophagy pathway takes an unconventional route

Selective autophagy transports specific cytoplasmic materials into lysosomes/vacuoles. In the case of macroautophagy the selectivity is mediated by receptors, which usually link the cargos to the machinery that sequesters them into the forming autophagosome. In our recent work, we found that fission yeast Nbr1, a homolog of the mammalian macroautophagy receptor NBR1, acts together with an unconventional autophagy-associated cargo sequestration apparatus, the endosomal sorting complexes required for transport (ESCRTs), to deliver 2 hydrolytic enzymes from the cytosol to the vacuole lumen. In this pathway, which we term the Nbr1-mediated vacuolar targeting (NVT) pathway, soluble cargos transit through the multi-vesicular body (MVB), rather than the autophagosome, on their way to the vacuole. Our findings reveal a novel mode of action of macroautophagy receptors and broaden our understanding of ESCRT-mediated autophagy.