Postfertilization Autophagy of Sperm Organelles Prevents Paternal Mitochondrial DNA Transmission

TLDR

In most animals, fertilization delivers sperm DNA and centrioles to the oocyte, but paternal mitochondria are normally eliminated by an as‑yet‑unknown degradation process. Sperm‑derived autophagosomes are recruited within minutes of fertilization, ubiquitinate sperm membranous organelles but not mitochondria, and LC3‑dependent autophagy subsequently degrades both paternal structures and mitochondrial DNA. The study demonstrates that fertilization triggers rapid LC3‑dependent autophagy that degrades paternal mitochondria and DNA in C.

Abstract

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.