Revealing mitochondrial function by reading mtDNA mutation patterns
Recent advances have provided is with gene editing strategies that allow an unprecedented ability to generate knock-out or knock-in animal models of nearly any desired nuclear encoded gene. Unfortunately, the mitochondrial DNA of animals remains resistant to these technologies. To circumvent this limitation, we utilize the mtDNA mutator mouse that expresses a proof-reading deficient mitochondrial DNA polymerase, leading to the accumulation of mitochondrial mutations. By applying different screening strategies to the mtDNA or mitochondrial RNAs, we look for the absence or enrichment of mtDNA mutations to elements involved in replication, transcription or transcript maturation.