Mammalian mitochondrial gene expression
in health and disease

Therefore, the life of mitochondrial RNAs from transcription through processing and maturation to protein synthesis is mediated by RNA-binding proteins, all located within the mitochondrial matrix. To date the link between transcription and translation in mammalian mitochondria is not well understood.

The mammalian mitochondrial genome is transcribed by the nuclear-encoded mitochondrial RNA polymerase (POLRMT), which acts with a couple of specialized transcription factors to synthesize mitochondrial transcripts. POLRMT also generates the RNA primers to initiate replication of the mitochondrial DNA placing this enzyme at the heart of both gene expression and replication in mitochondria. POLRMT is the sole mammalian mitochondrial RNA polymerase, and has thus, a central role in building a functional OXPHOS system. Indeed, since mitochondrial metabolism is intimately linked to the fate of cancer cells, POLRMT has recently been proposed as a target for drug development to treat cancers with elevated OXPHOS levels. Despite its fundamental cellular role, the in vivo function of POLRMT is far from being understood.

We previously generated large transcriptomics and proteomics data sets from several mouse models with different types of altered mitochondrial gene expression, leading to severe OXPHOS dysfunction in heart. As a consequence of defective gene expression in mitochondria we found extensive remodelling of the transcriptome and mito-proteome, and could identify several pathways altered in OXPHOS dysfunction (e.g. secondary coenzyme Q deficiency). Moreover, we identified specific expression patterns depending on the stage where mtDNA gene expression is affected. We are now interested in understanding underlying mechanisms with regard to regulation of mtDNA gene expression.