title: Selective endosomal microautophagy is starvation-inducible in Drosophila.
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.
authors.affiliation: a Department of Developmental and Molecular Biology , Albert Einstein College of Medicine , New York , NY , USA.
authors.forename: Anindita
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: a Department of Developmental and Molecular Biology , Albert Einstein College of Medicine , New York , NY , USA.
authors.forename: Bindi
authors.initials: B
authors.lastname: Patel
authors.affiliation: a Department of Developmental and Molecular Biology , Albert Einstein College of Medicine , New York , NY , USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koga
authors.affiliation: a Department of Developmental and Molecular Biology , Albert Einstein College of Medicine , New York , NY , USA.|b Institute for Aging Studies, Albert Einstein College of Medicine , New York , NY , USA.|c Marion Bessin Liver Research Center, Albert Einstein College of Medicine , New York , NY , USA.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
authors.affiliation: a Department of Developmental and Molecular Biology , Albert Einstein College of Medicine , New York , NY , USA.|b Institute for Aging Studies, Albert Einstein College of Medicine , New York , NY , USA.|c Marion Bessin Liver Research Center, Albert Einstein College of Medicine , New York , NY , USA.|d Department of Genetics , Albert Einstein College of Medicine , New York , NY , USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenny
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D057146:Multivesicular Bodies / Q000378:metabolism; D015398:Signal Transduction; D013217:Starvation / Q000473:pathology*
chemical_list: D015415:Biomarkers; D029721:Drosophila Proteins
keywords: Drosophila; Tor; autophagy; chaperone-mediated autophagy; endosomal microautophagy; proteostasis