In sexual reproduction of most animals, the spermatozoon provides DNA and centrioles, together with some cytoplasm and organelles, to the oocyte that is being fertilized. Paternal mitochondria and their genomes are generally eliminated in the embryo by an unknown degradation mechanism. We show that, upon fertilization, a Caenorhabditis elegans spermatozoon triggers the recruitment of autophagosomes within minutes and subsequent paternal mitochondria degradation. Whereas the nematode-specific sperm membranous organelles are ubiquitinated before autophagosome formation, the mitochondria are not. The degradation of both paternal structures and mitochondrial DNA requires an LC3-dependent autophagy. Analysis of fertilized mouse embryos shows the localization of autophagy markers, which suggests that this autophagy event is evolutionarily conserved to prevent both the transmission of paternal mitochondrial DNA to the offspring and the establishment of heteroplasmy.
SummaryEndosomes 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.
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