Reconsidering the selectivity of bulk autophagy: cargo hitchhiking specifies cargo for degradation.

Abstract

Bulk macroautophagy/autophagy, typically induced by starvation, is generally thought to non-selectively isolate cytosolic components for degradation. However, a detailed analysis of bulk autophagy cargo has not been conducted. We recently employed mass spectrometry to analyze the contents of isolated autophagic bodies. In this process, we uncovered Hab1 (Highly enriched in Autophagic Bodies 1), a novel protein, that is preferentially delivered via autophagy. Hab1 is a receptor protein that binds Atg8-PE and ribosomes at its N- and C-termini, respectively. We found that ribosome-bound Hab1 is preferentially delivered to the vacuole by "'hitchhiking'" on phagophores/isolation membranes formed during bulk autophagy. This hitchhiking mechanism confers selectivity to bulk autophagy.