Professor Nils-Göran Larsson

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholdm, Sweden

"How is mtDNA transcription regulated?"

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.