A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in
mitochondrial adaptations that accompany physiological cardiac hypertrophy.
Authors 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
Submitted By E. Dale Abel on 3/4/2015
Status Published
Journal Cell Metabolism
Year 2007
Date Published 10/1/2007
Volume : Pages 6 : 294 - 306
PubMed Reference 17908558
Abstract Physiological cardiac hypertrophy is associated with mitochondrial adaptations
that are characterized by activation of PGC-1alpha 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-1alpha. 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

Investigators with authorship
E. Dale AbelUniversity of Iowa
Adam WendeUniversity of Alabama at Birmingham