Asymmetric partitioning of persistent paternal mitochondria during cell divisions safeguards embryo development and mitochondrial inheritance

Most eukaryotes inherit only maternal mitochondria. The reasons for paternal mitochondrial elimination and the impacts of persistent paternal mitochondria on animals remain elusive. We show that undegraded paternal mitochondria in autophagy-deficient C. elegans embryos are gradually excluded from germ blastomeres through asymmetric partitioning during cell divisions. The embryonic cortical flow drives anterior-directed movements of paternal mitochondria and contributes to their asymmetric apportioning between two daughter blastomeres. By contrast, autophagosome-enclosed paternal mitochondria cluster around and segregate with centrosomes during mitosis and are rapidly degraded through lysosomes concentrated near centrosomes. Failure to exclude persistent paternal mitochondria from the germ blastomere at first cleavage causes their enrichment in the descendant endomesodermal (EMS) blastomere, leading to elevated reactive oxygen species levels, elongated EMS lineage durations, and increased embryonic lethality, which antioxidant treatments can suppress. Thus, regulated paternal mitochondrial distribution away from germ blastomeres is a fail-safe mechanism, protecting embryo development and maternal mitochondrial inheritance.