Egg MVBs elicit an antimicrobial pathway to degrade paternal mitochondria after fertilization

Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination (PME) after fertilization are far less clear. Using Drosophila , we show that special egg-derived multivesicular bodies (MVBs) promote PME by activating LC3-associated phagocytosis (LAP), a cellular defense pathway commonly employed against invading microbes. Upon fertilization, the egg MVBs engage and densely coat the sperm flagellum, forming extended flagellum vesicular sheaths (FVSs), within which the paternal mitochondria degrade. Inactivation of multiple LAP pathway components, such as Rubicon, a LAP-specific class III PI(3)K complex protein, significantly attenuates PME. Furthermore, recruitment of Atg8/LC3 to the FVS requires both Rubicon and the Atg8/LC3 conjugation machinery. Other LAP pathway events, such as production of the phospholipid PtdIns(3)P and reactive oxygen species (ROS), also unfold during PME. Finally, we provide evidence that a similar pathway might also mediate PME in mammals, highlighting the notion that eggs may regard paternal mitochondria as potentially dangerous trespassers.