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Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
1Correspondence: Washington University School of Medicine, Department of Medicine, Campus Box 8113, 4566 Scott Ave., St. Louis, MO 63110, USA. E-Mail: jhollosz{at}im.wustl.edu
Nuclear respiratory factor 1 (NRF-1) is a transcriptional activator of nuclear genes that encode a range of mitochondrial proteins including cytochrome c, various other respiratory chain subunits, and 
-aminolevulinate synthase. Activation of NRF-1 in fibroblasts has been shown to induce increases in cytochrome c expression and mitochondrial respiratory capacity. To further evaluate the role of NRF-1 in the regulation of mitochondrial biogenesis and respiratory capacity, we generated transgenic mice overexpressing NRF-1 in skeletal muscle. Cytochrome c expression was increased 
twofold and -aminolevulinate synthase was increased 50% in NRF-1 transgenic muscle. The levels of some mitochondrial proteins were increased 50–60%, while others were unchanged. Muscle respiratory capacity was not increased in the NRF-1 transgenic mice. A finding that provides new insight regarding the role of NRF-1 was that expression of MEF2A and GLUT4 was increased in NRF-1 transgenic muscle. The increase in GLUT4 was associated with a proportional increase in insulin-stimulated glucose transport. These results show that an isolated increase in NRF-1 is not sufficient to bring about a coordinated increase in expression of all of the proteins necessary for assembly of functional mitochondria. They also provide the new information that NRF-1 overexpression results in increased expression of GLUT4.—Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E,. Han, D.-H., Nolte, L. A., Ojuka, E. O., Chen, M., Holloszy, J. O. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity.
Key Words: -aminolevulinate synthase • cytochrome c • mitochondria • pyruvate oxidation • respiratory enzymes
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