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 journalArticle

78 Citations (Scopus)

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

Fingerprint

Nuclear Respiratory Factor 1
5-aminolevulinate synthase
Muscle
skeletal muscle
cytochrome c
Skeletal Muscle
genetically modified organisms
Glucose
glucose
muscles
Cytochromes c
proteins
mice
electron transport chain
Mitochondrial Proteins
fibroblasts
mitochondria
insulin
Transgenic Mice
Muscles

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

Cite this

Baar, K., Song, Z., Semenkovich, C. F., Jones, T. E., Han, D. H., Nolte, L. A., ... Holloszy, J. O. (2003). Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB Journal, 17(12), 1666-1673. https://doi.org/10.1096/fj.03-0049com

Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. / Baar, Keith; Song, Zheng; Semenkovich, Clay F.; Jones, Terry E.; Han, Dong Ho; Nolte, Lorraine A.; Ojuka, Edward O.; Chen, May; Holloszy, John O.

In: FASEB Journal, Vol. 17, No. 12, 09.2003, p. 1666-1673.

Research output: Contribution to journalArticle

Baar, K, Song, Z, Semenkovich, CF, Jones, TE, Han, DH, Nolte, LA, Ojuka, EO, Chen, M & Holloszy, JO 2003, 'Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity', FASEB Journal, vol. 17, no. 12, pp. 1666-1673. https://doi.org/10.1096/fj.03-0049com
Baar, Keith ; Song, Zheng ; Semenkovich, Clay F. ; Jones, Terry E. ; Han, Dong Ho ; Nolte, Lorraine A. ; Ojuka, Edward O. ; Chen, May ; Holloszy, John O. / Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. In: FASEB Journal. 2003 ; Vol. 17, No. 12. pp. 1666-1673.
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