Mitochondrial DNA polymerase gamma is expressed and translated in the absence of mitochondrial DNA maintenance and replication.
Mitochondria are essential organelles in all eukaryotic cells where cellular ATP is generated through the process of oxidative phosphorylation. Protein components of the respiratory assembly are gene products of both mitochondrial and nuclear genes. The mitochondrial genome itself encodes several protein and nucleic acid components required for such oxidative phosphorylative processes, but the vast majority of genes encoding respiratory chain components are nuclear. Similarly, the processes of replication and transcription of mitochondrial DNA rely exclusively upon RNA and protein species encoded by nuclear genes. We have analyzed two key nuclear-encoded proteins involved in mitochondrial DNA replication and transcription as a function of the presence or absence of mitochondrial DNA. Mitochondrial DNA polymerase (DNA polymerase gamma), the nuclear-encoded enzyme which synthesizes mtDNA, is expressed and translated in cells devoid of mitochondrial DNA itself. In contrast, mitochondrial transcription factor A protein levels are tightly linked to the mtDNA status of the cell. These results demonstrate that the DNA polymerase gamma protein is stable in the absence of mitochondrial DNA, and that there appears to be no regulatory mechanism present in these cells to alter levels of this protein in the complete absence of mitochondrial DNA. Alternatively, it is possible that this enzyme plays an additional, as yet undefined, role in the cell, thereby mandating its continued production.
Davis
A F
AF
Department of Developmental Biology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine 94305-5427, USA.
Ropp
P A
PA
Clayton
D A
DA
Copeland
W C
WC
D001483:Base Sequence; D004258:DNA Polymerase III / Q000096:biosynthesis / Q000235:genetics*; D017931:DNA Primers; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins
D017931:DNA Primers; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C499631:TFAM protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C097078:XL-MTTFA protein, Xenopus; D029867:Xenopus Proteins; C422562:mitochondrial transcription factor A; D004258:DNA Polymerase III