The Mitochondrial Transcription Machinery

Abstract

The involvement of mitochondria in multiple cellular functions beyond generation of ATP creates a need to organize mitochondrial DNA and regulate transcription of mitochondrial genes. The mitochondrial transcription apparatus itself is encoded in the nuclear genome. The central component of this apparatus- the mitochondrial RNA polymerase (mtRNAP)-is homologous to the single-subunit RNAPs encoded by multiple bacteriophages, most notably the well-characterized RNAP encoded by the T7 bacteriophage. Biophysical and biochemical studies have revealed that structure-mechanism relationships are remarkably well-conserved between the phage and mitochondrial RNAPs, with homologous elements in both polymerase classes playing similar roles in promoter recognition, bending, melting, and transcription initiation. However, mtRNAPs are distinct from phage RNAPs, because mtRNAPs in isolation assume a "clenched" conformation in which the large DNA-binding cleft of the polymerase is occluded and other parts of the polymerase involved in promoter binding are sequestered by intramolecular interactions. Interactions between the mtRNAP and mitochondrial transcription factors alter mtRNAP structure to relieve this intramolecular sequestration and unlock the promoter-specific binding and transcriptional activity of the polymerase. There is one such factor required for mitochondrial transcription initiation in yeast and two required factors in mammalian mitochondria, which may allow for greater scope in regulation in higher vs. lower eukaryotes. Thus, mitochondrial transcription relies on an RNAP that is homologous to the phage RNAPs that can function without any accessory factors but exhibits features analogous to nuclear or bacterial transcription in that it requires additional factors to specifically initiate transcription at mitochondrial promoters. In this review, we aim to provide a comprehensive description of the general, common mitochondrial transcription mechanisms and of the variations in these transcription systems, from Saccharomyces cerevisiae to Homo sapiens.