Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number

► We review TFAM-DNA interactions, including specificity, affinity, bending, and cooperativity. ► We review proposed mechanisms of TFAM regulation of mtDNA copy number. ► We propose a model in which TFAM dimerization, DNA looping, and cooperativity impact mtDNA packaging and promoter activity.