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  Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione

Kürschner, G., Zhang, Q., Clima, R., Xiao, Y., Busch, J. F., Kilic, E., et al. (2017). Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione. Oncotarget, 2017: 8:105882-105904. doi:10.18632/oncotarget.22413.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-918D-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-918E-6
Genre: Journal Article

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 Creators:
Kürschner, Gerrit1, 2, Author
Zhang, Qingzhou , Author
Clima, Rosanna , Author
Xiao , Yi1, 3, Author
Busch, Jonas Felix , Author
Kilic, Ergin , Author
Jung, Klaus, Author
Berndt, Nikolaus , Author
Bulik, Sascha , Author
Holzhütter, Hermann-Georg , Author
Gasparre, Giuseppe , Author
Attimonelli, Marcella , Author
Babu, Mohan , Author
Meierhofer, David1, Author              
Affiliations:
1Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
2Technical University of Berlin, Institute of Bioanalytics, Department of Biotechnology, Berlin, Germany, ou_persistent22              
3Freie Universität Berlin, Fachbereich Biologie, Chemie, Pharmazie, Berlin, Germany, ou_persistent22              

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Free keywords: renal oncocytoma; complex I deficiency; glutathione metabolism; mtDNA mutation
 Abstract: Renal oncocytomas are rare benign tumors of the kidney and characterized by a deficient complex I (CI) enzyme activity of the oxidative phosphorylation (OXPHOS) system caused by mitochondrial DNA (mtDNA) mutations. Yet, little is known about the underlying molecular mechanisms and alterations of metabolic pathways in this tumor. We compared renal oncocytomas with adjacent matched normal kidney tissues on a global scale by multi-omics approaches, including whole exome sequencing (WES), proteomics, metabolomics, and metabolic pathway simulation. The abundance of proteins localized to mitochondria increased more than 2-fold, the only exception was a strong decrease in the abundance for CI subunits that revealed several pathogenic heteroplasmic mtDNA mutations by WES. We also observed renal oncocytomas to dysregulate main metabolic pathways, shunting away from gluconeogenesis and lipid metabolism. Nevertheless, the abundance of energy carrier molecules such as NAD+, NADH, NADP, ATP, and ADP were significantly higher in renal oncocytomas. Finally, a substantial 5000-fold increase of the reactive oxygen species scavenger glutathione can be regarded as a new hallmark of renal oncocytoma. Our findings demonstrate that renal oncocytomas undergo a metabolic switch to eliminate ATP consuming processes to ensure a sufficient energy supply for the tumor.

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Language(s): eng - English
 Dates: 2017-09-212017-11-11
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.18632/oncotarget.22413
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Title: Oncotarget
Source Genre: Journal
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Pages: - Volume / Issue: 2017 Sequence Number: 8:105882-105904 Start / End Page: - Identifier: ISSN: 1949-2553
CoNE: /journals/resource/1949-2553