title: Induction of autophagy in ESCRT mutants is an adaptive response for cell survival in C. elegans.
abstract: Endosomes and autophagosomes are two vesicular compartments involved in the degradation and recycling of cellular material. They both undergo a maturation process and finally fuse with the lysosome. In mammals, the convergence between endosomes and autophagosomes is a multistep process that can generate intermediate vesicles named amphisomes. Using knockdowns and mutants of the ESCRT machinery (ESCRT-0-ESCRT-III, ATPase VPS-4) and the autophagic pathway (LGG-1, LGG-2, ATG-7, TOR), we analyzed in vivo the functional links between endosomal maturation and autophagy in Caenorhabditis elegans. We report here that, despite a strong heterogeneity of their developmental phenotypes, all ESCRT mutants present an accumulation of abnormal endosomes and autophagosomes. We show that this accumulation of autophagosomes is secondary to the formation of enlarged endosomes and is due to the induction of the autophagic flux and not a blockage of fusion with lysosomes. We demonstrate that the induction of autophagy is not responsible for the lethality of ESCRT mutants but has a protective role on cellular degradation. We also show that increasing the basal level of autophagy reduces the formation of enlarged endosomes in ESCRT mutants. Together, our data indicate that the induction of autophagy is a protective response against the formation of an abnormal vesicular compartment.
authors.affiliation: Centre de Génétique Moléculaire, UPR 3404, CNRS, Associée à l'université Paris-Sud XI, FRC3115, Avenue de terrasse, Gif-sur-Yvette, 91198, France.
authors.forename: Abderazak
authors.initials: A
authors.lastname: Djeddi
authors.forename: Xavier
authors.initials: X
authors.lastname: Michelet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Culetto
authors.forename: Adriana
authors.initials: A
authors.lastname: Alberti
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barois
authors.forename: Renaud
authors.initials: R
authors.lastname: Legouis
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics* / Q000502:physiology; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017238:Genes, Helminth; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D056827:Endosomal Sorting Complexes Required for Transport