Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis

Mitochondrial transcription factor A (Tfam) is required for mtDNA maintenan ce, 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 Tf am mRNA isoforms as spermatogenesis proceeds in both mouse and man. Interes tingly, an abundant testis-specific nuclear Tfam protein isoform of unknown function is found in the mouse, but not in humans. We have now characteriz ed Tfam expression in rat testis to identify conserved features in mammalia n spermatogenesis. The nuclear Tfam protein isoform, is absent in the rat a nd is thus dispensable for mammalian spermatogenesis. Similar to mice and h umans, 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 transmi ssion.