| First Author | Klawitter J | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 10540 |
| PubMed ID | 28874678 | Mgi Jnum | J:255464 |
| Mgi Id | MGI:6109243 | Doi | 10.1038/s41598-017-10076-9 |
| Citation | Klawitter J, et al. (2017) Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney. Sci Rep 7(1):10540 |
| abstractText | The mitochondrial matrix protein cyclophilin D (CypD) is an essential component of the mitochondrial permeability transition pore (MPTP). Here we characterized the effects of CypD ablation on bioenergetics in the kidney. CypD loss triggers a metabolic shift in Ppif-/- male and female mouse kidneys towards glycolysis and Krebs cycle activity. The shift is accompanied by increased glucose consumption and a transcriptional upregulation of effectors of glucose metabolism in the kidney. These included activation of Akt, AMPK (only in males) and p70S6K kinases. Gender specific differences between the Ppif-/- male and female mouse kidneys were observed including activation of pro-surviving ERK1/2 kinase and inhibited expression of pro-apoptotic and pro-fibrotic JNK and TGFbeta1 proteins in Ppif-/- females. They also showed the highest expression of phosphorylated-ERK1/2 and Akt S473 proteins of all four investigated animal groups. Furthermore, Ppif-/- females showed higher lactate concentrations and ATP/ADP-ratios in the kidney than males. These metabolic and transcriptional modifications could provide an additional level of protection to Ppif-/- females. In summary, loss of mitochondrial CypD results in a shift in bioenergetics and in activation of glucose-metabolism regulating Akt/AMPK/p70S6 kinase pathways that is expected to affect the capability of Ppif-/- mice kidneys to react to stimuli and injury. |
