RRC ID 46066
著者 Djeddi A, Michelet X, Culetto E, Alberti A, Barois N, Legouis R.
タイトル Induction of autophagy in ESCRT mutants is an adaptive response for cell survival in C. elegans.
ジャーナル J Cell Sci
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.
巻・号 125(Pt 3)
ページ 685-94
公開日 2012-2-1
DOI 10.1242/jcs.091702
PII 125/3/685
PMID 22389403
MeSH Adaptation, Physiological Animals Animals, Genetically Modified Autophagy / genetics* Autophagy / physiology Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Survival / genetics Cell Survival / physiology Endosomal Sorting Complexes Required for Transport / antagonists & inhibitors Endosomal Sorting Complexes Required for Transport / genetics* Endosomal Sorting Complexes Required for Transport / metabolism Endosomes / metabolism Gene Knockdown Techniques Genes, Helminth Mutation Phenotype RNA Interference
IF 4.573
引用数 37
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm1483 tm3200