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Shalgi et al. 1994 ; Sutovsky et al. 1996 ). Thus, mitochondria from the sperm enter
the embryo, but their contribution to the mitochondrial pool in the zygote is minimal,
if any. One contributing factor is simply the minuscule contribution of sperm-
derived mitochondria to the mitochondrial pool in the zygote. The mouse oocyte
contains ~10^5 mitochondria (Piko and Matsumoto 1976 ), which provides a huge
excess over less than hundred mitochondria in the midpiece (Ankel-Simons and
Cummins 1996 ). Furthermore, paternal mitochondria are actively degraded in the
zygote (reviewed in Cummins 2000 ).
Both ubiquitination and autophagy were implicated in paternal mitochondria
destruction in animals. In mammals, Sutovsky et al. noted ubiquitination of the
bovine sperm mitochondria inside oocyte cytoplasm and proteolysis during pre-
implantation development (Sutovsky et al. 1999 ). According to their model,
mitochondrial membrane proteins are already tagged with ubiquitin in haploid
spermatocytes, hence allowing their recognition in the zygote, and subsequent
targeting for polyubiquitination and destruction might involve proteasome activ-
ity or autophagy (mitophagy) or both. It was also found that degradation of por-
cine sperm mitochondria is sensitive to proteasome inhibitor MG132 (Sutovsky
et al. 2003 ), while tracking of bovine sperm mitochondria suggested association
with lysosomes (Sutovsky et al. 2000 ). However, tracking autophagosomes and
sperm mitochondria during early development challenged the role of autophagy
in clearance of paternal mitochondria (Luo et al. 2013b). The current view is
that mammals might employ a two-way mechanism of sperm mitochondria deg-
radation involving both proteasomal and lysosomal proteolysis (Song et al.
2014 ). Of note is that studies in Drosophila and C. elegans demonstrated involve-
ment of autophagy in degradation of paternal mitochondria (Politi et al. 2014 ;
Sato and Sato 2011 ; Al Rawi et al. 2011 ).
Finally, another layer of regulation preventing the transmission of sperm-
derived mtDNA to the offspring can be active digestion of the paternal mtDNA
in the mitochondria. A study from Oryzias latipes (Japanese rice fish, medaka
fish) showed that digestion of paternal mtDNA takes place before the destruc-
tion of the sperm mitochondrial body (Nishimura et al. 2006 ). The nuclease
responsible for this digestion has not yet been identified. Whether this mecha-
nism exists across vertebrates is unclear; there is no indication that paternal
mitochondrial DNA would be degraded before the mitochondrial body in mice
(Hecht et al. 1984 ).
Acknowledgment We thank members of the Laboratory of Epigenetic Regulations at the
Institute of Molecular Genetics (AS CR) for their help with the manuscript preparation,
Vedran Franke and Kristian Vlahovicek for their continuous help with high-throughput data
analysis, and Richard M. Schultz for his useful discussions. The main support for studying
early development in the Laboratory of Epigenetic Regulations is provided by the Czech
Science Foundation (grant GACR P305/12/G034); the Czech Ministry of Education, Youth
and Sports (project NPU I LO1419 Biomodels4Health); and the European Research Council
Consolidator project D-FENS.
P. Svoboda et al.