Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we
lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular
rates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. We
undertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Following
this, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration of
other nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels and
available [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, or
higher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also found
evidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughter
studies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria at
division. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters have
relatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability in
transcription rate.