Mitochondrial gene expression is regulated at the level of transcription during early embryogenesis of Xenopus laevis

Mitochondrial transcription in the early Xenopus laevis embryo resumes seve ral hours before active mtDNA replication, effectively decoupling mtDNA tra nscription and replication. This developmental feature makes Xenopus embryo genesis an appealing model system to investigate the regulation of mitochon drial transcription. Studies reported here refine our understanding of the timing, magnitude, and mechanism of this transcriptional induction event. N orthern analyses of six mitochondrial mRNAs (normalized to mtDNA) reveal th at transcript levels remain basal between fertilization and gastrulation an d then undergo a coordinate induction, culminating in a 20-28-fold increase over egg levels by 48 h of development. Measurement of mitochondrial run-o n transcription rates demonstrates a good correlation between transcription rates and transcript levels, showing that transcription itself is the prim ary determinant of transcript abundance. Experimental increases in mitochon drial ATP and energy charge also correlate with patterns of transcript leve ls and transcription rates, suggesting that developmental changes in the bi ochemical composition of the mitochondrial matrix could be regulating trans criptional activity. Consistent with this idea, transcriptional run-on rate s in mitochondria of early embryos can be stimulated by the addition of tri carboxylic acid cycle intermediates to the run on reaction. However, mitoch ondria of later stages do not show this response to the addition of metabol ite. In combination, these data suggest that mitochondrial transcription is under metabolic regulation during early Xenopus embryogenesis.