Selective endosomal microautophagy is starvation-inducible inDrosophila

Aug 4, 2016Autophagy

Starvation triggers selective recycling inside cells in fruit flies

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Abstract

A novel, starvation-inducible catabolic process resembling endosomal microautophagy has been identified in Drosophila melanogaster.

The KFERQ-tagged fluorescent biosensor localizes to late endosomes and lysosomes during prolonged starvation.
This eMI-like pathway is dependent on KFERQ motifs and the chaperone Hsc70-4.
Induction of eMI requires longer starvation periods compared to macroautophagy.
The process is independent of critical macroautophagy genes atg5, atg7, and atg12.
Inhibition of Tor signaling can induce eMI in nutrient-rich conditions.
The genes atg1 and atg13 may have a novel role in regulating eMI in Drosophila.

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Autophagy delivers cytosolic components to lysosomes for degradation and is thus essential for cellular homeostasis and to cope with different stressors. As such, autophagy counteracts various human diseases and its reduction leads to aging-like phenotypes. Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, whereas selective degradation of single proteins has only been described for chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI). These 2 autophagic pathways are specific for proteins containing KFERQ-related targeting motifs. Using a KFERQ-tagged fluorescent biosensor, we have identified an eMI-like pathway in Drosophila melanogaster. We show that this biosensor localizes to late endosomes and lysosomes upon prolonged starvation in a KFERQ- and Hsc70-4- dependent manner. Furthermore, fly eMI requires endosomal multivesicular body formation mediated by ESCRT complex components. Importantly, induction of Drosophila eMI requires longer starvation than the induction of MA and is independent of the critical MA genes atg5, atg7, and atg12. Furthermore, inhibition of Tor signaling induces eMI in flies under nutrient rich conditions, and, as eMI in Drosophila also requires atg1 and atg13, our data suggest that these genes may have a novel, additional role in regulating eMI in flies. Overall, our data provide the first evidence for a novel, starvation-inducible, catabolic process resembling endosomal microautophagy in the Drosophila fat body.

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Selective endosomal microautophagy is starvation-inducible inDrosophila

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