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Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.

Publication ,  Journal Article
Ahuja, P; Zhao, P; Angelis, E; Ruan, H; Korge, P; Olson, A; Wang, Y; Jin, ES; Jeffrey, FM; Portman, M; Maclellan, WR
Published in: J Clin Invest
May 2010

In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPARgamma coactivator-1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity and fatty acid oxidation genes in preference for glucose metabolism pathways. Interestingly, despite the reduced PGC-1 activity, these pathological stressors are associated with mitochondrial biogenesis, at least initially. The transcription factors that regulate these changes in the setting of reduced PGC-1 are unknown, but Myc can regulate glucose metabolism and mitochondrial biogenesis during cell proliferation and tumorigenesis in cancer cells. Here we have demonstrated that Myc activation in the myocardium of adult mice increases glucose uptake and utilization, downregulates fatty acid oxidation by reducing PGC-1alpha levels, and induces mitochondrial biogenesis. Inactivation of Myc in the adult myocardium attenuated hypertrophic growth and decreased the expression of glycolytic and mitochondrial biogenesis genes in response to hemodynamic load. Surprisingly, the Myc-orchestrated metabolic alterations were associated with preserved cardiac function and improved recovery from ischemia. Our data suggest that Myc directly regulates glucose metabolism and mitochondrial biogenesis in cardiac myocytes and is an important regulator of energy metabolism in the heart in response to pathologic stress.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 2010

Volume

120

Issue

5

Start / End Page

1494 / 1505

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • Oxygen
  • Neoplasms
  • Myocytes, Cardiac
  • Myocardial Ischemia
  • Mitochondria
  • Mice, Transgenic
 

Citation

APA
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MLA
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Ahuja, P., Zhao, P., Angelis, E., Ruan, H., Korge, P., Olson, A., … Maclellan, W. R. (2010). Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Invest, 120(5), 1494–1505. https://doi.org/10.1172/JCI38331
Ahuja, Preeti, Peng Zhao, Ekaterini Angelis, Hongmei Ruan, Paavo Korge, Aaron Olson, Yibin Wang, et al. “Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.J Clin Invest 120, no. 5 (May 2010): 1494–1505. https://doi.org/10.1172/JCI38331.
Ahuja P, Zhao P, Angelis E, Ruan H, Korge P, Olson A, et al. Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Invest. 2010 May;120(5):1494–505.
Ahuja, Preeti, et al. “Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice.J Clin Invest, vol. 120, no. 5, May 2010, pp. 1494–505. Pubmed, doi:10.1172/JCI38331.
Ahuja P, Zhao P, Angelis E, Ruan H, Korge P, Olson A, Wang Y, Jin ES, Jeffrey FM, Portman M, Maclellan WR. Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Invest. 2010 May;120(5):1494–1505.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

May 2010

Volume

120

Issue

5

Start / End Page

1494 / 1505

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • Oxygen
  • Neoplasms
  • Myocytes, Cardiac
  • Myocardial Ischemia
  • Mitochondria
  • Mice, Transgenic