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A new activating role for CO in cardiac mitochondrial biogenesis.
J Cell Sci. 2007 Jan 15; 120(Pt 2):299-308.JC

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17179207

Citation

Suliman, Hagit B., et al. "A New Activating Role for CO in Cardiac Mitochondrial Biogenesis." Journal of Cell Science, vol. 120, no. Pt 2, 2007, pp. 299-308.
Suliman HB, Carraway MS, Tatro LG, et al. A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci. 2007;120(Pt 2):299-308.
Suliman, H. B., Carraway, M. S., Tatro, L. G., & Piantadosi, C. A. (2007). A new activating role for CO in cardiac mitochondrial biogenesis. Journal of Cell Science, 120(Pt 2), 299-308.
Suliman HB, et al. A New Activating Role for CO in Cardiac Mitochondrial Biogenesis. J Cell Sci. 2007 Jan 15;120(Pt 2):299-308. PubMed PMID: 17179207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new activating role for CO in cardiac mitochondrial biogenesis. AU - Suliman,Hagit B, AU - Carraway,Martha S, AU - Tatro,Lynn G, AU - Piantadosi,Claude A, Y1 - 2006/12/19/ PY - 2006/12/21/pubmed PY - 2007/4/12/medline PY - 2006/12/21/entrez SP - 299 EP - 308 JF - Journal of cell science JO - J. Cell. Sci. VL - 120 IS - Pt 2 N2 - 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. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/17179207/A_new_activating_role_for_CO_in_cardiac_mitochondrial_biogenesis_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=17179207 DB - PRIME DP - Unbound Medicine ER -