Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
Abstract 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...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/855d8a990d7643ce85d334b9efe5b799 |
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| Sumario: | Abstract 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 TGFβ1 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. |
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