The NRFs, in turn, activate the mitochondrial transcription factor A (tfam), which is directly responsible for transcribing nuclear-encoded mitochondrial proteins.
Nrf1, together with Nrf2, mediates the biogenomic coordination between nuclear and mitochondrial genomes by directly regulating the expression of several nuclear-encoded ETC proteins, and indirectly regulating the three mitochondrial-encoded COX subunit genes by activating mtTFA, mtTFB1, and mtTFB2.