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A new activating role for CO in cardiac mitochondrial biogenesis.

Publication ,  Journal Article
Suliman, HB; Carraway, MS; Tatro, LG; Piantadosi, CA
Published in: J Cell Sci
January 15, 2007

To investigate a possible new physiological role of carbon monoxide (CO), an endogenous gas involved in cell signaling and cytotoxicity, we tested the hypothesis that the mitochondrial generation of reactive oxygen species by CO activates mitochondrial biogenesis in the heart. In mice, transient elevations of cellular CO by five- to 20-fold increased the copy number of cardiac mitochondrial DNA, the content of respiratory complex I-V and interfibrillar mitochondrial density within 24 hours. Mitochondrial biogenesis is activated by gene and protein expression of the nuclear respiratory factor 1 (NRF1) and NRF2, of peroxisome proliferator-activated receptor gamma co-activator-1alpha, and of mitochondrial transcription factor A (TFAM), which augmented the copy number of mitochondrial DNA (mtDNA). This is independent of nitric oxide synthase (NOS), as demonstrated by the identical responses in wild-type and endothelial NOS (eNOS)-deficient mice, and by the inhibition of inducible NOS (iNOS). In the heart and in isolated cardiomyocytes, CO activation involved both guanylate cyclase and the pro-survival kinase Akt/PKB. Akt activation was facilitated by mitochondrial binding of CO and by production of hydrogen peroxide (H(2)O(2)). Interference with Akt activity by blocking PI 3-kinase and by mitochondrial targeting of catalase to scavenge H(2)O(2) prevented binding of NRF1 to the Tfam promoter, thereby connecting mitochondrial H(2)O(2) to the pathway leading to mtDNA replication. The findings disclose mitochondrial CO and H(2)O(2) as new activating factors in cardiac mitochondrial biogenesis.

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Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

January 15, 2007

Volume

120

Issue

Pt 2

Start / End Page

299 / 308

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transcription Factors
  • Trans-Activators
  • Time Factors
  • Reactive Oxygen Species
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Nuclear Respiratory Factor 1
 

Citation

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Suliman, H. B., Carraway, M. S., Tatro, L. G., & Piantadosi, C. A. (2007). A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci, 120(Pt 2), 299–308. https://doi.org/10.1242/jcs.03318
Suliman, Hagit B., Martha S. Carraway, Lynn G. Tatro, and Claude A. Piantadosi. “A new activating role for CO in cardiac mitochondrial biogenesis.J Cell Sci 120, no. Pt 2 (January 15, 2007): 299–308. https://doi.org/10.1242/jcs.03318.
Suliman HB, Carraway MS, Tatro LG, Piantadosi CA. A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci. 2007 Jan 15;120(Pt 2):299–308.
Suliman, Hagit B., et al. “A new activating role for CO in cardiac mitochondrial biogenesis.J Cell Sci, vol. 120, no. Pt 2, Jan. 2007, pp. 299–308. Pubmed, doi:10.1242/jcs.03318.
Suliman HB, Carraway MS, Tatro LG, Piantadosi CA. A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci. 2007 Jan 15;120(Pt 2):299–308.
Journal cover image

Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

January 15, 2007

Volume

120

Issue

Pt 2

Start / End Page

299 / 308

Location

England

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transcription Factors
  • Trans-Activators
  • Time Factors
  • Reactive Oxygen Species
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Nuclear Respiratory Factor 1