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Insulin and Growth Factor Regulation of Cardiac Mitochondria
Author(s) -
Abel E. Dale
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a91-e
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , mitochondrion , muscle hypertrophy , signal transduction , akt1 , growth factor , biology , oxidative phosphorylation , chemistry , endocrinology , biochemistry , receptor
Physiological cardiac hypertrophy is mediated by various signals such as growth factors, and is associated with mitochondrial remodeling characterized by activation of PGC‐1α and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphoinositide‐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 have observed that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial remodeling in response to physiological hypertrophic stimuli despite increased expression of PGC1‐α. We also observed that activation of the downstream kinase Akt is not required for the mitochondrial remodeling due 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 metabolic and mitochondrial adaptations.