| First Author | Li C | Year | 2013 |
| Journal | Free Radic Biol Med | Volume | 60 |
| Pages | 29-40 | PubMed ID | 23376468 |
| Mgi Jnum | J:201239 | Mgi Id | MGI:5512824 |
| Doi | 10.1016/j.freeradbiomed.2013.01.013 | Citation | Li C, et al. (2013) PI3K/AKT signaling regulates bioenergetics in immortalized hepatocytes. Free Radic Biol Med 60:29-40 |
| abstractText | Regulation of cellular bioenergetics by PI3K/AKT signaling was examined in isogenic hepatocyte cell lines lacking the major inhibitor of PI3K/AKT signaling, PTEN (phosphatase and tensin homolog deleted on chromosome 10). PI3K/AKT signaling was manipulated using the activator (IGF-1) and the inhibitor (LY 294002) of the PI3K/AKT pathway. Activation of PI3K/AKT signaling resulted in an enhanced anaerobic glycolysis and mitochondrial respiration. AKT, when phosphorylated and activated, translocated to mitochondria and localized within the membrane structure of mitochondria, where it phosphorylated a number of mitochondrial-resident proteins including the subunits alpha and beta of ATP synthase. Inhibition of GSK3beta by either phosphorylation by AKT or lithium chloride resulted in activation of pyruvate dehydrogenase, i.e., a decrease in its phosphorylated form. AKT-dependent phosphorylation of ATP synthase subunits alpha and beta resulted in an increased complex activity. AKT translocation to mitochondria was associated with an increased expression and activity of complex I. These data suggest that the mitochondrial signaling pathway AKT/GSK3beta/PDH, AKT-dependent phosphorylation of ATP synthase, and upregulation of mitochondrial complex I expression and activity are involved in the control of mitochondrial bioenergetics by increasing substrate availability and regulating the mitochondrial catalytic/energy-transducing capacity. |
