Mitochondrial Transcription Is Regulated via an ATP “Sensing” Mechanism that Couples RNA Abundance to Respiration

Abstract

The information encoded in both the nuclear and mitochondrial genomes must be coordinately regulated to respond to changes in cellular growth and energy states. Despite identification of the mitochondrial RNA polymerase (mtRNAP) from several organisms, little is known about mitochondrial transcriptional regulation. Studying the shift from fermentation to respiration in Saccharomyces cerevisiae, we have demonstrated a direct correlation between in vivo changes in mitochondrial transcript abundance and in vitro sensitivity of mitochondrial promoters to ATP concentration (K(m)ATP). Consistent with the idea that the mtRNAP itself senses in vivo ATP levels, we found that transcript abundance correlates with respiration, but only when coupled to mitochondrial ATP synthesis. In addition, we characterized mutations in the mitochondrial promoter and the mtRNAP accessory factor Mtf1 that alter both in vitro K(m)ATP and in vivo transcription in response to respiratory changes. We propose that shifting cellular pools of ATP coordinately control nuclear and mitochondrial transcription.