A Tissue-Specific and Temporally-Regulated Autophagic Switch Controls a Drosophila Nutritional Checkpoint

Properly timed production of steroid hormones by endocrine tissues regulates juvenile-to-adult transitions in both mammals (puberty) and holometabolous insects (metamorphosis). Nutritional conditions influence the temporal control of the transition, but the mechanisms responsible are ill-defined. Here we demonstrate that autophagy acts as an endocrine organ-specific, nutritionally-regulated, gating mechanism to help ensure productive metamorphosis in Drosophila. Autophagy in the endocrine organ is specifically stimulated by nutrient restriction (NR) at the early, but not the late L3 stage, which suppresses precocious metamorphosis in undersized larvae. Induction of autophagy disrupts production of the steroid hormone ecdysone not by destruction of biosynthetic capacity, but rather by limiting the availability of the steroid hormone precursor cholesterol. Interestingly, autophagy functions by interacting with endo/lysosome system, yet shows multiple features not fully consistent with a canonical autophagy process. Taken together, our findings demonstrate an autophagy mechanism in endocrine cells that helps guarantee a successful juvenile-to-adult transition in animals confronting nutritional stress.