Transcription and replication of mtDNA are dependent on nuclear-encoded transcription and replication factors that translocate to the mitochondrial genome to first transcribe and then replicate mtDNA (33, 35). The key factors involved are mitochondrial transcription factor A that initiates transcription that then results in the generation of a primer that is used by the catalytic subunit of the mtDNA-specific polymerase (polymerase gamma A; POLGA) to copy mtDNA. The process is supported by POLGB, the accessory subunit to POLGA and by the mitochondrial-specific single stranded binding protein (mtSSB) and helicase (Twinkle).