How is mtDNA transcription regulated?

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• Professor Nils-Göran Larsson, Karolinska Institute
• Thursday 24 November 2022, 15:00-16:00
• MRC MBU, Level 7 Lecture Theatre, The Keith Peters Building, CB2 0XY.

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A single copy of mammalian mtDNA is compacted by binding of ~1000 copies mitochondrial transcription factor A (TFAM) to form the mitochondrial nucleoid. The compaction of the nucleoid varies, and transcription has been reported to occur from its less compacted form. The TFAM to-mtDNA ratio influences nucleoid compaction in vitro and in vivo, but the mechanism controlling this regulation of compaction remains obscure. Transcription initiation of mammalian mtDNA requires the bacteriophage-like mitochondrial RNA polymerase (POLRMT), TFAM and one additional factor, whereas the switch to transcription elongation requires that POLRMT interacts with a third factor. The transcription system in mammalian mitochondria is thus very simple and distinct from the much more complex systems in the nucleus. We have performed a range of biochemical and genetic experiments in the mouse and the results are consistent with a model where regulation of mtDNA gene expression is mainly dependent on posttranscriptional mechanisms. Furthermore, our results argue that the synthesis of nucleus-encoded OXPHOS subunits is not closely correlated with the synthesis of mtDNA-encoded subunits. Instead, proteolytic degradation of excess OXPHOS subunits seems to adjust the balance so that the levels of nucleus and mtDNA-encoded subunits match when the OXPHOS complexes are formed.

This talk is part of the MRC Mitochondrial Biology Unit Seminars series.

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