Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity

Keith Baar, Zheng Song, Clay F. Semenkovich, Terry E. Jones, Dong Ho Han, Lorraine A. Nolte, Edward O. Ojuka, May Chen, John O. Holloszy

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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 δ -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 δ-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.

Original languageEnglish (US)
Pages (from-to)1666-1673
Number of pages8
JournalFASEB Journal
Volume17
Issue number12
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • δ-aminolevulinate synthase
  • Cytochrome c
  • Mitochondria
  • Pyruvate oxidation
  • Respiratory enzymes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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