Selective endosomal microautophagy is starvation-inducible in Drosophila

Anindita Mukherjee, Bindi Patel, Hiroshi Koga, Ana Maria Cuervo, Andreas Jenny

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalAutophagy
DOIs
StateAccepted/In press - Nov 1 2016

Keywords

  • autophagy
  • chaperone-mediated autophagy
  • Drosophila
  • endosomal microautophagy
  • proteostasis
  • Tor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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