An intruder-targeting system eliminates paternal mitochondria after fertilization in Drosophila

Maternal inheritance of mitochondria occurs in almost all organisms, spanning from fungi and plants to humans. Upon fertilization, a single sperm fully penetrates the egg, resulting in a short period where mitochondria from both gametes populate the early embryo. Within a few cell cycles, however, paternal mitochondria (PM) are eliminated, and propagating maternal mitochondria take over the mitochondrial network. Several reports illustrate PM elimination as an outcome of passive dilution by the vast maternal mitochondrial pool. Yet, recent studies performed on different organisms suggest active elimination of PM by egg-derived mechanisms. In particular, our group previously demonstrated that egg-derived multi-vesicular bodies (MVBs) associate with PM immediately after fertilization to promote PM degradation. Nevertheless, the mechanisms by which MVBs mediate paternal mitochondrial destruction remain unknown.

Here, I will present our recent findings aiming to identify the mechanisms by which egg-derived MVBs target and destroy PM in Drosophila. We identify a cell intruder-targeting pathway, called LC3-associated phagocytosis (LAP), which is a common endocytic, autophagic and phagocytic pathway, as the main executer of PM elimination. Our model indicates that MVBs loaded with LAP-specific components engage with PM to mediate its elimination. LAP-specific phosphatidylinositol 3-phosphate kinase (PI3K) complex is recruited to PM for PI3P production. The presence of PI3P, together with generation of ROS, promote Atg8 (LC3) conjugation to PM, facilitating sequestration of PM to lysosomes. Finally, I will also present initial evidence for possible conservation of some of these mechanisms during corresponding processes in mammalian eggs.