TitleSelective endosomal microautophagy is starvation-inducible in Drosophila.
Publication TypeJournal Article
Year of Publication2016
AuthorsMukherjee A, Patel B, Koga H, Cuervo AMaria, Jenny A
Date Published2016 Nov
KeywordsAmino Acid Motifs, Animals, Autophagy, Biomarkers, Drosophila melanogaster, Drosophila Proteins, Endosomes, Lysosomes, Multivesicular Bodies, Signal Transduction, Starvation

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.

Alternate JournalAutophagy
PubMed ID27487474
PubMed Central IDPMC5103356
Grant ListP30 DK041296 / DK / NIDDK NIH HHS / United States
R21 AG046805 / AG / NIA NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
P30 AG038072 / AG / NIA NIH HHS / United States
R01 DK098408 / DK / NIDDK NIH HHS / United States
P30 CA013330 / CA / NCI NIH HHS / United States
P01 AG031782 / AG / NIA NIH HHS / United States