A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy

Brian T. O'Neill, Jaetaek Kim, Adam R. Wende, Heather A. Theobald, Joseph Tuinei, Jonathan Buchanan, Aili Guo, Vlad G. Zaha, Don K. Davis, John C. Schell, Sihem Boudina, Benjamin Wayment, Sheldon E. Litwin, Tetsuo Shioi, Seigo Izumo, Morris J. Birnbaum, E. Dale Abel

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1α and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1α. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.

Original languageEnglish (US)
Pages (from-to)294-306
Number of pages13
JournalCell Metabolism
Volume6
Issue number4
DOIs
StatePublished - Oct 3 2007

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Phosphatidylinositol 3-Kinase
Physiological Adaptation
Cardiomegaly
Growth
Fatty Acids
Hypertrophy
Phosphotransferases

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy. / O'Neill, Brian T.; Kim, Jaetaek; Wende, Adam R.; Theobald, Heather A.; Tuinei, Joseph; Buchanan, Jonathan; Guo, Aili; Zaha, Vlad G.; Davis, Don K.; Schell, John C.; Boudina, Sihem; Wayment, Benjamin; Litwin, Sheldon E.; Shioi, Tetsuo; Izumo, Seigo; Birnbaum, Morris J.; Abel, E. Dale.

In: Cell Metabolism, Vol. 6, No. 4, 03.10.2007, p. 294-306.

Research output: Contribution to journalArticle

O'Neill, BT, Kim, J, Wende, AR, Theobald, HA, Tuinei, J, Buchanan, J, Guo, A, Zaha, VG, Davis, DK, Schell, JC, Boudina, S, Wayment, B, Litwin, SE, Shioi, T, Izumo, S, Birnbaum, MJ & Abel, ED 2007, 'A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy', Cell Metabolism, vol. 6, no. 4, pp. 294-306. https://doi.org/10.1016/j.cmet.2007.09.001
O'Neill, Brian T. ; Kim, Jaetaek ; Wende, Adam R. ; Theobald, Heather A. ; Tuinei, Joseph ; Buchanan, Jonathan ; Guo, Aili ; Zaha, Vlad G. ; Davis, Don K. ; Schell, John C. ; Boudina, Sihem ; Wayment, Benjamin ; Litwin, Sheldon E. ; Shioi, Tetsuo ; Izumo, Seigo ; Birnbaum, Morris J. ; Abel, E. Dale. / A Conserved Role for Phosphatidylinositol 3-Kinase but Not Akt Signaling in Mitochondrial Adaptations that Accompany Physiological Cardiac Hypertrophy. In: Cell Metabolism. 2007 ; Vol. 6, No. 4. pp. 294-306.
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