Accessorizing the human mitochondrial transcription machinery

• Mitochondrial RNA polymerase (POLRMT), TFB2M (transcription factor B2, mitochondrial), and TFAM (transcription factor A, mitochondrial) provide basal regulation of human mitochondrial transcription.
• Structures of key mitochondrial transcription components have provided new insights.
• The need to understand regulation of mitochondrial transcription in vivo is eminent.
• Accessory factors provide additional layers of mitochondrial transcriptional regulation.

The human genome comprises large chromosomes in the nucleus and mitochondrial DNA (mtDNA) housed in the dynamic mitochondrial network. Human cells contain up to thousands of copies of the double-stranded, circular mtDNA molecule that encodes essential subunits of the oxidative phosphorylation complexes and the rRNAs and tRNAs needed to translate these in the organelle matrix. Transcription of human mtDNA is directed by a single-subunit RNA polymerase, POLRMT, which requires two primary transcription factors, TFB2M (transcription factor B2, mitochondrial) and TFAM (transcription factor A, mitochondrial), to achieve basal regulation of the system. Here, we review recent advances in understanding the structure and function of the primary human transcription machinery and the other factors that facilitate steps in transcription beyond initiation and provide more intricate control over the system.