REGULATION OF ATP SYNTHASE SUBUNIT-E GENE-EXPRESSION BY HYPOXIA - CELL-DIFFERENTIATION STAGE-SPECIFIC CONTROL

Using the technique of differential display, we identified genes that are expressed differentially under normoxic and hypoxic conditions. On e regulated gene encoded subunit e of mitochondrial F1F0-ATP synthase (subunit e). The hypoxia-mediated regulation of subunit e expression i n C2C12 cells was influenced by the stage of cellular differentiation. Under normoxic conditions, subunit e expression was markedly upregula ted during the transition from myoblast to myotube. After exposure to hypoxia for 24 h, subunit e mRNA expression markedly decreased (>70%) in C2C12 myotubes. In contrast, subunit e mRNA levels increased slight ly in response to hypoxia in C2C12 myoblasts. Studies performed with p rimary rat cardiocytes demonstrated that expression of subunit e mRNA and a cardiac-enriched related transcript was downregulated after a hy poxic exposure. We conclude that expression of subunit e is regulated, at the pretranslational level, by oxygen availability via cell differ entiation stage-specific mechanisms consistent with the proposed regul atory role of this protein in cellular ATP production.