Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury

Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or...
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Autor*in:	Adam J. Rauckhorst [verfasserIn] Gabriela Vasquez Martinez [verfasserIn] Gabriel Mayoral Andrade [verfasserIn] Hsiang Wen [verfasserIn] Ji Young Kim [verfasserIn] Aaron Simoni [verfasserIn] Claudia Robles-Planells [verfasserIn] Kranti A. Mapuskar [verfasserIn] Prerna Rastogi [verfasserIn] Emily J. Steinbach [verfasserIn] Michael L. McCormick [verfasserIn] Bryan G. Allen [verfasserIn] Navjot S. Pabla [verfasserIn] Ashley R. Jackson [verfasserIn] Mitchell C. Coleman [verfasserIn] Douglas R. Spitz [verfasserIn] Eric B. Taylor [verfasserIn] Diana Zepeda-Orozco [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress

Übergeordnetes Werk:	In: Molecular Metabolism - Elsevier, 2015, 79(2024), Seite 101849-
Übergeordnetes Werk:	volume:79 ; year:2024 ; pages:101849-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.molmet.2023.101849

Katalog-ID:	DOAJ096286113

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245	1	0	\|a Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
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520			\|a Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.
650		4	\|a Acute kidney injury
650		4	\|a Hormesis
650		4	\|a Metabolomics
650		4	\|a Mitochondrial metabolism
650		4	\|a Oxidative stress
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700	0		\|a Gabriela Vasquez Martinez \|e verfasserin \|4 aut
700	0		\|a Gabriel Mayoral Andrade \|e verfasserin \|4 aut
700	0		\|a Hsiang Wen \|e verfasserin \|4 aut
700	0		\|a Ji Young Kim \|e verfasserin \|4 aut
700	0		\|a Aaron Simoni \|e verfasserin \|4 aut
700	0		\|a Claudia Robles-Planells \|e verfasserin \|4 aut
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700	0		\|a Ashley R. Jackson \|e verfasserin \|4 aut
700	0		\|a Mitchell C. Coleman \|e verfasserin \|4 aut
700	0		\|a Douglas R. Spitz \|e verfasserin \|4 aut
700	0		\|a Eric B. Taylor \|e verfasserin \|4 aut
700	0		\|a Diana Zepeda-Orozco \|e verfasserin \|4 aut
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allfields	10.1016/j.molmet.2023.101849 doi (DE-627)DOAJ096286113 (DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07 DE-627 ger DE-627 rakwb eng RC31-1245 Adam J. Rauckhorst verfasserin aut Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity. Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine Gabriela Vasquez Martinez verfasserin aut Gabriel Mayoral Andrade verfasserin aut Hsiang Wen verfasserin aut Ji Young Kim verfasserin aut Aaron Simoni verfasserin aut Claudia Robles-Planells verfasserin aut Kranti A. Mapuskar verfasserin aut Prerna Rastogi verfasserin aut Emily J. Steinbach verfasserin aut Michael L. McCormick verfasserin aut Bryan G. Allen verfasserin aut Navjot S. Pabla verfasserin aut Ashley R. Jackson verfasserin aut Mitchell C. Coleman verfasserin aut Douglas R. Spitz verfasserin aut Eric B. Taylor verfasserin aut Diana Zepeda-Orozco verfasserin aut In Molecular Metabolism Elsevier, 2015 79(2024), Seite 101849- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:79 year:2024 pages:101849- https://doi.org/10.1016/j.molmet.2023.101849 kostenfrei https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877823001837 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 79 2024 101849-
spelling	10.1016/j.molmet.2023.101849 doi (DE-627)DOAJ096286113 (DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07 DE-627 ger DE-627 rakwb eng RC31-1245 Adam J. Rauckhorst verfasserin aut Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity. Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine Gabriela Vasquez Martinez verfasserin aut Gabriel Mayoral Andrade verfasserin aut Hsiang Wen verfasserin aut Ji Young Kim verfasserin aut Aaron Simoni verfasserin aut Claudia Robles-Planells verfasserin aut Kranti A. Mapuskar verfasserin aut Prerna Rastogi verfasserin aut Emily J. Steinbach verfasserin aut Michael L. McCormick verfasserin aut Bryan G. Allen verfasserin aut Navjot S. Pabla verfasserin aut Ashley R. Jackson verfasserin aut Mitchell C. Coleman verfasserin aut Douglas R. Spitz verfasserin aut Eric B. Taylor verfasserin aut Diana Zepeda-Orozco verfasserin aut In Molecular Metabolism Elsevier, 2015 79(2024), Seite 101849- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:79 year:2024 pages:101849- https://doi.org/10.1016/j.molmet.2023.101849 kostenfrei https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877823001837 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 79 2024 101849-
allfields_unstemmed	10.1016/j.molmet.2023.101849 doi (DE-627)DOAJ096286113 (DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07 DE-627 ger DE-627 rakwb eng RC31-1245 Adam J. Rauckhorst verfasserin aut Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity. Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine Gabriela Vasquez Martinez verfasserin aut Gabriel Mayoral Andrade verfasserin aut Hsiang Wen verfasserin aut Ji Young Kim verfasserin aut Aaron Simoni verfasserin aut Claudia Robles-Planells verfasserin aut Kranti A. Mapuskar verfasserin aut Prerna Rastogi verfasserin aut Emily J. Steinbach verfasserin aut Michael L. McCormick verfasserin aut Bryan G. Allen verfasserin aut Navjot S. Pabla verfasserin aut Ashley R. Jackson verfasserin aut Mitchell C. Coleman verfasserin aut Douglas R. Spitz verfasserin aut Eric B. Taylor verfasserin aut Diana Zepeda-Orozco verfasserin aut In Molecular Metabolism Elsevier, 2015 79(2024), Seite 101849- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:79 year:2024 pages:101849- https://doi.org/10.1016/j.molmet.2023.101849 kostenfrei https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877823001837 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 79 2024 101849-
allfieldsGer	10.1016/j.molmet.2023.101849 doi (DE-627)DOAJ096286113 (DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07 DE-627 ger DE-627 rakwb eng RC31-1245 Adam J. Rauckhorst verfasserin aut Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity. Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine Gabriela Vasquez Martinez verfasserin aut Gabriel Mayoral Andrade verfasserin aut Hsiang Wen verfasserin aut Ji Young Kim verfasserin aut Aaron Simoni verfasserin aut Claudia Robles-Planells verfasserin aut Kranti A. Mapuskar verfasserin aut Prerna Rastogi verfasserin aut Emily J. Steinbach verfasserin aut Michael L. McCormick verfasserin aut Bryan G. Allen verfasserin aut Navjot S. Pabla verfasserin aut Ashley R. Jackson verfasserin aut Mitchell C. Coleman verfasserin aut Douglas R. Spitz verfasserin aut Eric B. Taylor verfasserin aut Diana Zepeda-Orozco verfasserin aut In Molecular Metabolism Elsevier, 2015 79(2024), Seite 101849- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:79 year:2024 pages:101849- https://doi.org/10.1016/j.molmet.2023.101849 kostenfrei https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877823001837 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 79 2024 101849-
allfieldsSound	10.1016/j.molmet.2023.101849 doi (DE-627)DOAJ096286113 (DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07 DE-627 ger DE-627 rakwb eng RC31-1245 Adam J. Rauckhorst verfasserin aut Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity. Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine Gabriela Vasquez Martinez verfasserin aut Gabriel Mayoral Andrade verfasserin aut Hsiang Wen verfasserin aut Ji Young Kim verfasserin aut Aaron Simoni verfasserin aut Claudia Robles-Planells verfasserin aut Kranti A. Mapuskar verfasserin aut Prerna Rastogi verfasserin aut Emily J. Steinbach verfasserin aut Michael L. McCormick verfasserin aut Bryan G. Allen verfasserin aut Navjot S. Pabla verfasserin aut Ashley R. Jackson verfasserin aut Mitchell C. Coleman verfasserin aut Douglas R. Spitz verfasserin aut Eric B. Taylor verfasserin aut Diana Zepeda-Orozco verfasserin aut In Molecular Metabolism Elsevier, 2015 79(2024), Seite 101849- (DE-627)739898752 (DE-600)2708735-9 22128778 nnns volume:79 year:2024 pages:101849- https://doi.org/10.1016/j.molmet.2023.101849 kostenfrei https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 kostenfrei http://www.sciencedirect.com/science/article/pii/S2212877823001837 kostenfrei https://doaj.org/toc/2212-8778 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 79 2024 101849-
language	English
source	In Molecular Metabolism 79(2024), Seite 101849- volume:79 year:2024 pages:101849-
sourceStr	In Molecular Metabolism 79(2024), Seite 101849- volume:79 year:2024 pages:101849-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress Internal medicine
isfreeaccess_bool	true
container_title	Molecular Metabolism
authorswithroles_txt_mv	Adam J. Rauckhorst @@aut@@ Gabriela Vasquez Martinez @@aut@@ Gabriel Mayoral Andrade @@aut@@ Hsiang Wen @@aut@@ Ji Young Kim @@aut@@ Aaron Simoni @@aut@@ Claudia Robles-Planells @@aut@@ Kranti A. Mapuskar @@aut@@ Prerna Rastogi @@aut@@ Emily J. Steinbach @@aut@@ Michael L. McCormick @@aut@@ Bryan G. Allen @@aut@@ Navjot S. Pabla @@aut@@ Ashley R. Jackson @@aut@@ Mitchell C. Coleman @@aut@@ Douglas R. Spitz @@aut@@ Eric B. Taylor @@aut@@ Diana Zepeda-Orozco @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	739898752
id	DOAJ096286113
language_de	englisch
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Rauckhorst</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. 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callnumber-first	R - Medicine
author	Adam J. Rauckhorst
spellingShingle	Adam J. Rauckhorst misc RC31-1245 misc Acute kidney injury misc Hormesis misc Metabolomics misc Mitochondrial metabolism misc Oxidative stress misc Internal medicine Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
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topic_title	RC31-1245 Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury Acute kidney injury Hormesis Metabolomics Mitochondrial metabolism Oxidative stress
topic	misc RC31-1245 misc Acute kidney injury misc Hormesis misc Metabolomics misc Mitochondrial metabolism misc Oxidative stress misc Internal medicine
topic_unstemmed	misc RC31-1245 misc Acute kidney injury misc Hormesis misc Metabolomics misc Mitochondrial metabolism misc Oxidative stress misc Internal medicine
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title	Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
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title_full	Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
author_sort	Adam J. Rauckhorst
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author_browse	Adam J. Rauckhorst Gabriela Vasquez Martinez Gabriel Mayoral Andrade Hsiang Wen Ji Young Kim Aaron Simoni Claudia Robles-Planells Kranti A. Mapuskar Prerna Rastogi Emily J. Steinbach Michael L. McCormick Bryan G. Allen Navjot S. Pabla Ashley R. Jackson Mitchell C. Coleman Douglas R. Spitz Eric B. Taylor Diana Zepeda-Orozco
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title_sort	tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
callnumber	RC31-1245
title_auth	Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
abstract	Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.
abstractGer	Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.
abstract_unstemmed	Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. This raises the possibility of therapeutically modulating the MPC to attenuate AKI severity.
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title_short	Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury
url	https://doi.org/10.1016/j.molmet.2023.101849 https://doaj.org/article/3fd3e25948fb47dd89066773a4e94c07 http://www.sciencedirect.com/science/article/pii/S2212877823001837 https://doaj.org/toc/2212-8778
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doi_str	10.1016/j.molmet.2023.101849
callnumber-a	RC31-1245
up_date	2024-07-03T19:18:52.868Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">DOAJ096286113</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240413145908.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240413s2024 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.molmet.2023.101849</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ096286113</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ3fd3e25948fb47dd89066773a4e94c07</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC31-1245</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Adam J. Rauckhorst</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Objective: Energy-intensive kidney reabsorption processes essential for normal whole-body function are maintained by tubular epithelial cell metabolism. Although tubular metabolism changes markedly following acute kidney injury (AKI), it remains unclear which metabolic alterations are beneficial or detrimental. By analyzing large-scale, publicly available datasets, we observed that AKI consistently leads to downregulation of the mitochondrial pyruvate carrier (MPC). This investigation aimed to understand the contribution of the tubular MPC to kidney function, metabolism, and acute injury severity. Methods: We generated tubular epithelial cell-specific Mpc1 knockout (MPC TubKO) mice and employed renal function tests, in vivo renal 13C-glucose tracing, mechanistic enzyme activity assays, and tests of injury and survival in an established rhabdomyolysis model of AKI. Results: MPC TubKO mice retained normal kidney function, displayed unchanged markers of kidney injury, but exhibited coordinately increased enzyme activities of the pentose phosphate pathway and the glutathione and thioredoxin oxidant defense systems. Following rhabdomyolysis-induced AKI, compared to WT control mice, MPC TubKO mice showed increased glycolysis, decreased kidney injury and oxidative stress markers, and strikingly increased survival. Conclusions: Our findings suggest that decreased renal tubular mitochondrial pyruvate uptake hormetically upregulates oxidant defense systems before AKI and is a beneficial adaptive response after rhabdomyolysis-induced AKI. 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Tubular mitochondrial pyruvate carrier disruption elicits redox adaptations that protect from acute kidney injury

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