A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro.
Human mitochondrial transcription factor A is a 25-kDa protein that binds immediately upstream of the two major mitochondrial promoters, thereby leading to correct and efficient initiation of transcription. Although the nature of yeast mitochondrial promoters is significantly different from that of human promoters, a potential functional homolog of the human transcriptional activator protein has been previously identified in yeast mitochondria. The importance of the yeast protein in yeast mitochondrial DNA function has been shown by inactivation of its nuclear gene (ABF2) in Saccharomyces cerevisiae cells resulting in loss of mitochondrial DNA. We report here that the nuclear gene for human mitochondrial transcription factor A can be stably expressed in yeast cells devoid of the yeast homolog protein. The human protein is imported efficiently into yeast mitochondria, is processed correctly, and rescues the loss-of-mitochondrial DNA phenotype in a yeast abf2 strain, thus functionally substituting for the yeast protein. Both human and yeast proteins affect yeast mitochondrial transcription initiation in vitro, suggesting that the two proteins may have a common role in this fundamental process.
Parisi
M A
MA
Department of Developmental Biology, Stanford University School of Medicine, California 94305-5427.
Xu
B
B
Clayton
D A
DA
D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D002451:Cell Compartmentation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005796:Genes; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010101:Oxygen Consumption / Q000235:genetics; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014170:Transformation, Genetic
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; C499631:TFAM protein, human; D014157:Transcription Factors; C422562:mitochondrial transcription factor A