Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control.

1. Mitochondrial ATP synthesis (oxidative phosphorylation) is mainly regulated by the membrane potential (respiratory control) and protein synthesis (transcriptional control). 2. According to the current view, genes for enzymes of oxidative phosphorylation are classified as housekeeping genes that are transcribed constitutively. These genes have been sequenced. 3. Four complexes of oxidative phosphorylation (complexes I, III and IV, and ATP synthase) are exceptional oligomers that contain subunits encoded by mitochondrial DNA. The remaining subunits of these complexes, as well as thousands of other mammalian enzymes are encoded by nuclear DNA. 4. It is proposed that ATP synthase (F0F1) and these oligomers supplying energy to F0F1, though they are housekeeping, are under some coordinated transcriptional control. Not transcription, but translation of mitochondrial DNA is mainly regulated. 5. Recently, studies on cloned human genes for the FoF1 beta subunit and 7 enzymes related to ATP synthesis revealed coordinated transcription. Moreover, a novel common cis-element (enhancer) was discovered in the 5'-upstream region of genes for the F1 beta subunit, cytochrome c1 and pyruvate dehydrogenase E1 alpha subunit. 6. In contrast to heme control and catabolite repression of yeast via trans-acting elements such as HAP and GP, signal transduction and coordinated transcription of human oxidative phosphorylation is not directed by CP1 (a HAP homolog), but may be closely related to cell differentiation.