title: Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis.
abstract: Mitochondrial transcription factor A (Tfam) is required for mtDNA maintenance, and mitochondrial Tfam protein levels directly affect mtDNA copy number. Previous studies have shown significant reduction of Tfam protein levels in mitochondria together with the appearance of abundant testis-specific Tfam mRNA isoforms as spermatogenesis proceeds in both mouse and man. Interestingly, an abundant testis-specific nuclear Tfam protein isoform of unknown function is found in the mouse, but not in humans. We have now characterized Tfam expression in rat testis to identify conserved features in mammalian spermatogenesis. The nuclear Tfam protein isoform is absent in the rat and is thus dispensable for mammalian spermatogenesis. Similar to mice and humans, we found expression of alternate Tfam transcripts, downregulation of mitochondrial Tfam protein levels, and downregulation of mtDNA copy number during rat spermatogenesis. These features are thus common to all mammals and may provide one of several mechanisms preventing paternal mtDNA transmission.
authors.affiliation: Department of Medical Nutrition, Karolinska Institutet, Novum, Huddinge Hospital, S-14186 Huddinge, 76 Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Rantanen
authors.forename: M
authors.initials: M
authors.lastname: Jansson
authors.forename: A
authors.initials: A
authors.lastname: Oldfors
authors.forename: N G
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017124:Conserved Sequence / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005091:Exons / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C499631:TFAM protein, human; C081930:Tfam protein, mouse; C489030:Tfam protein, rat; D014157:Transcription Factors; C422562:mitochondrial transcription factor A