Regulation of mitochondrial DNA copy number during spermatogenesis.
The nuclear genome is physically compacted during spermatogenesis by replacing histones with protamines and transition proteins. This altered nuclear protein context may make gene regulation at the transcriptional level less efficient and could explain why post-transcriptional regulation is prominent in haploid male germ cells. Mitochondria and mitochondrial (mt) DNA are maternally inherited, whereas the transmission of paternal mtDNA is blocked in mammals. The paternal mtDNA enters the oocyte but is no longer detectable in the preimplantation embryo. Several mechanisms could be responsible for preventing the transmission of paternal mtDNA, including the down-regulation of mtDNA copy number during spermatogenesis, specific elimination of paternal mitochondria in fertilized oocytes, and the suspension of mtDNA replication in the fertilized oocyte. It is the first of these that is the subject of the present review. Mitochondrial transcription factor A (mtTFA, or Tfam) is a key regulator of mtDNA copy number in mammals. Germ cell-specific Tfam transcript isoforms are expressed during spermatogenesis in mice and humans. These alternative Tfam transcript isoforms have a structure that could prevent protein translation; their expression coincides with down-regulation of the mitochondrial Tfam protein values. We propose that this down-regulation of mitochondrial Tfam protein levels in turn down-regulates mtDNA copy number during mammalian spermatogenesis.
Rantanen
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A
Department of Molecular Medicine, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Larsson
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NG
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005111:Extrachromosomal Inheritance / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins; D006801:Humans; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000502:physiology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology; D029867:Xenopus Proteins
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C499631:TFAM protein, human; C081930:Tfam protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C097078:XL-MTTFA protein, Xenopus; D029867:Xenopus Proteins; C422562:mitochondrial transcription factor A