Promoter analysis of the human succinate dehydrogenase iron-protein gene--both nuclear respiratory factors NRF-1 and NRF-2 are required.

The iron-sulfur subunit of succinate dehydrogenase is one of the four subunits of complex II of the mitochondrial electron transport chain. Its gene, SDH2, is one of the four nuclear-encoded genes for this complex. Reporter gene analysis of the human SDH2 promoter indicates that it is transcriptionally regulated by the nuclear respiratory factors NRF-1 and NRF-2. Their binding sites reside immediately upstream (within 90 bp) of the transcription start site. Site-directed mutagenesis of either site lowers the reporter gene activity by tenfold to a basal level. Gel shift experiments and competition experiments with the authentic NRF-1 and NRF-2 DNA oligomers from previously characterized nuclear respiratory genes strengthen the proposed role of these two transcriptional regulators. These experiments extend the proposed regulatory role of these two transcription factors to complex II of the respiratory chain. The expression of three of the four genes of complex II was also examined when mouse myoblast C2C12 cells were induced to differentiate into myotubes. Up-regulation upon differentiation in tissue culture is only modest, 2-3 fold over the myoblast cells.