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bioRxiv · 10.1101/2025.03.18.642775

Multiple pathways prevent bi-parental mitochondria transmission in C. elegans

Abstract

The uniparental transmission of the maternal mitochondrial genome is achieved by the disposal of the sperm mitochondria and their DNA (mtDNA) around fertilization. C. elegans embryo allowed the identification of several factors and mechanisms involved after fertilization. The discovery that the autophagy pathway and its adaptor ALLO-1 are implicated represented a major progress. In addition, studies in fish and fly have implicated CPS-6, a sperm mitochondrial endonuclease, in the degradation of C. elegans sperm-derived mtDNA. The sperm mitochondria-associated proteins FNDC-1 and PHB-2 were also implicated in efficiently removing sperm-derived mitochondria. Despite these recent findings, it is still not clear whether they account for the complete degradation and if we can experimentally prevent sperm-mitochondria clearance and induce sperm-mtDNA transmission to the progeny. Here, we investigated the genetic interactions and tested the impact of simultaneous inactivation of known factors on the fate of sperm-derived mitochondria and their mtDNA. We revealed an additive effect of ALLO-1 and CPS-6 loss of function. Furthermore, the inactivation of known factors acting in sperm mitochondria clearance was not sufficient to avoid sperm mitochondria removal and to allow paternal mtDNA inheritance across generations. These findings reveal that C. elegans employs at least two parallel pathways to ensure the degradation of paternal mitochondria and suggest the presence of unidentified mechanism(s) safeguarding maternal mitochondrial inheritance.

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Melin, V., Cailloce, J., Husson, F., Merlet, J., Galy, V.. 2025-03-18. Multiple pathways prevent bi-parental mitochondria transmission in C. elegans. https://doi.org/10.1101/2025.03.18.642775

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