Control of unconventional secretion by the autophagy machinery

Autophagy is a highly conserved and critical recycling and degradation pathway that involves the selective engulfment of cytoplasmic organelles and proteins into double-membrane vesicles termed autophagosomes that subsequently fuse with lysosomes for degradation. In addition to its established role in protein degradation, there is a growing body of evidence that in response to specific environmental cues, the autophagy machinery promotes unconventional secretion of leaderless proteins via diverse mechanisms, collectively termed ‘secretory autophagy’. In this review, we describe recent findings highlighting these noncanonical functions of the autophagy machinery in specifying vesicular cargo loading for secretion and discuss how secretory autophagy is regulated during a wide range of cellular stresses, including inflammation, starvation, and lysosomal damage.