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:	Jelena Klawitter, Alexander Pennington, Jost Klawitter, Joshua M. Thurman, Uwe Christians
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/855d8a990d7643ce85d334b9efe5b799
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spelling	oai:doaj.org-article:855d8a990d7643ce85d334b9efe5b7992021-12-02T15:06:14ZMitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney10.1038/s41598-017-10076-92045-2322https://doaj.org/article/855d8a990d7643ce85d334b9efe5b7992017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-10076-9https://doaj.org/toc/2045-2322Abstract 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.Jelena KlawitterAlexander PenningtonJost KlawitterJoshua M. ThurmanUwe ChristiansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jelena Klawitter Alexander Pennington Jost Klawitter Joshua M. Thurman Uwe Christians Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
description	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.
format	article
author	Jelena Klawitter Alexander Pennington Jost Klawitter Joshua M. Thurman Uwe Christians
author_facet	Jelena Klawitter Alexander Pennington Jost Klawitter Joshua M. Thurman Uwe Christians
author_sort	Jelena Klawitter
title	Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
title_short	Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
title_full	Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
title_fullStr	Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
title_full_unstemmed	Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney
title_sort	mitochondrial cyclophilin d ablation is associated with the activation of akt/p70s6k pathway in the mouse kidney
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/855d8a990d7643ce85d334b9efe5b799
work_keys_str_mv	AT jelenaklawitter mitochondrialcyclophilindablationisassociatedwiththeactivationofaktp70s6kpathwayinthemousekidney AT alexanderpennington mitochondrialcyclophilindablationisassociatedwiththeactivationofaktp70s6kpathwayinthemousekidney AT jostklawitter mitochondrialcyclophilindablationisassociatedwiththeactivationofaktp70s6kpathwayinthemousekidney AT joshuamthurman mitochondrialcyclophilindablationisassociatedwiththeactivationofaktp70s6kpathwayinthemousekidney AT uwechristians mitochondrialcyclophilindablationisassociatedwiththeactivationofaktp70s6kpathwayinthemousekidney
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Mitochondrial cyclophilin D ablation is associated with the activation of Akt/p70S6K pathway in the mouse kidney

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