Unique insights into maternal mitochondrial inheritance in mice

Area of Science:

• Reproductive Biology
• Cellular Biology
• Genetics

Background:

• Mitochondrial DNA (mtDNA) is typically maternally inherited in animals.
• Autophagy was recently implicated in paternal mitochondrial elimination in C. elegans and suggested in mice.
• P62 and LC3 proteins, markers of autophagy, were observed with sperm mitochondria post-fertilization in mice.

Purpose of the Study:

• To investigate the role of autophagy in the elimination of paternal mitochondria and mtDNA after fertilization in mice.
• To determine the mechanism underlying maternal inheritance of mtDNA in mice.

Main Methods:

• Utilized two transgenic mouse strains: one with GFP-labeled autophagosomes and another with red fluorescent protein-labeled mitochondria.
• Employed immunofluorescence to observe P62 and LC3 protein localization.
• Conducted single sperm mtDNA PCR to analyze mtDNA content in sperm and early embryos.

Main Results:

• Autophagy was not involved in the post-fertilization elimination of sperm mitochondria in mice.
• Sperm mitochondria, despite initial P62/LC3 association, were not degraded by autophagy.
• Sperm mitochondria exhibited uneven distribution during early embryonic cleavage, persisting until the morula stage.
• Most motile sperm reaching the oviduct had already eliminated their mtDNA prior to fertilization.
• If sperm with intact mtDNA entered the zygote, it was not eliminated and was detectable in newborn mice.

Conclusions:

• Maternal inheritance of mtDNA in mice is a passive process, not an active elimination via autophagy in early embryos.
• Prefertilization elimination of sperm mtDNA and uneven mitochondrial distribution are key factors in ensuring maternal mtDNA inheritance.