Mitochondrial transcription factor A (Tfam) binds to and organizes mitochondrial DNA (mtDNA) genome into a mitochondrial nucleoid (mt-nucleoid) structure, which is necessary for mtDNA transcription and maintenance. Here, we demonstrate the mtDNA-organizing activity of mouse Tfam and its transcript isoform (Tfamiso), which has a smaller high-mobility group (HMG)-box1 domain, using a yeast model system that contains a deletion of the yeast homolog of mouse Tfam protein, Abf2p. When the mouse Tfam genes were introduced into the ABF2 locus of yeast genome, the corresponding mouse proteins, Tfam and Tfamiso, can functionally replace the yeast Abf2p and support mtDNA maintenance and mitochondrial biogenesis in yeast. Growth properties, mtDNA content and mitochondrial protein levels of genes encoded in the mtDNA were comparable in the strains expressing mouse proteins and the wild-type yeast strain, indicating that the proteins have robust mtDNA-maintaining and -expressing function in yeast mitochondria. These results imply that the mtDNA-organizing activities of the mouse mt-nucleoid proteins are structurally and evolutionary conserved, thus they can maintain the mtDNA of distantly related and distinctively different species, such as yeast.
Bibliographical noteFunding Information:
This work was supported by NIH grant NS052612 , the Minnesota Medical Foundation , the Academic Health Center and the Institute of Human Genetics of the University of Minnesota to MDK and the National Research Foundation of Korea Grant ( 2011 0001262 ) funded by the Korean Government. We would like to thank Drs. Thomas D. Fox and Kathleen Conklin for the gift of the yeast strains.
- Mitochondrial nucleoid
- Mitochondrial transcription factor A
- Transcript isoform