English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma

Mayr, J. A., Meierhofer, D., Zimmermann, F., Feichtinger, R., Kögler, C., Ratschek, M., et al. (2008). Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma. Clinical Cancer Research, 14(8), 2270-2275. doi:10.1158/1078-0432.CCR-07-4131.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-7E67-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-7E68-8
Genre: Journal Article

Files

show Files
hide Files
:
Mayr.pdf (Publisher version), 349KB
Name:
Mayr.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2008 American Association for Cancer Research
License:
-

Locators

show

Creators

show
hide
 Creators:
Mayr, Johannes A.1, Author
Meierhofer, David1, 2, Author              
Zimmermann, Franz1, Author
Feichtinger, Rene1, Author
Kögler, Christian, Author
Ratschek, Manfred, Author
Schmeller, Nikolaus, Author
Sperl, Wolfgang1, Author
Kofler, Barbara1, Author
Affiliations:
1Departments of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria, ou_persistent22              
2Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

Content

show
hide
Free keywords: oncocytoma, complex I, respiratory chain, mitochondrial DNA
 Abstract: Purpose: Many solid tumors exhibit abnormal aerobic metabolism characterized by increased glycolytic capacity and decreased cellular respiration. Recently, mutations in the nuclear encoded mitochondrial enzymes fumarate hydratase and succinate dehydrogenase have been identified in certain tumor types, thus demonstrating a direct link between mitochondrial energy metabolism and tumorigenesis. Although mutations in the mitochondrial genome (mitochondrial DNA, mtDNA) also can affect aerobic metabolism and mtDNA alterations are frequently observed in tumor cells, evidence linking respiratory chain deficiency in a specific tumor type to a specific mtDNA mutation has been lacking. Experimental Design: To identify mitochondrial alterations in oncocytomas, we investigated the activities of respiratory chain enzymes and sequenced mtDNA in 15 renal oncocytoma tissues. Results: Here, we show that loss of respiratory chain complex I (NADH/ubiquinone oxidoreductase) is associated with renal oncocytoma. Enzymatic activity of complex I was undetectable or greatly reduced in the tumor samples (n = 15). Blue Native gel electrophoresis of the multisubunit enzyme complex revealed a lack of assembled complex I. Mutation analysis of the mtDNA showed frame-shift mutations in the genes of either subunit ND1, ND4, or ND5 of complex I in 9 of the 15 tumors. Conclusion: Our data indicate that isolated loss of complex I is a specific feature of renal oncocytoma and that this deficiency is frequently caused by somatic mtDNA mutations.

Details

show
hide
Language(s): eng - English
 Dates: 2008-04-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1158/1078-0432.CCR-07-4131
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Clinical Cancer Research
  Other : Clin. Cancer Res.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Denville, NJ : Association for Cancer Research
Pages: - Volume / Issue: 14 (8) Sequence Number: - Start / End Page: 2270 - 2275 Identifier: ISSN: 1078-0432
CoNE: https://pure.mpg.de/cone/journals/resource/954925605818