Document Detail


Metabolic control analysis of cellular respiration in situ in intraoperational samples of human breast cancer.
MedLine Citation:
PMID:  22836527     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The aim of this study was to analyze quantitatively cellular respiration in intraoperational tissue samples taken from human breast cancer (BC) patients. We used oxygraphy and the permeabilized cell techniques in combination with Metabolic Control Analysis (MCA) to measure a corresponding flux control coefficient (FCC). The activity of all components of ATP synthasome, and respiratory chain complexes was found to be significantly increased in human BC cells in situ as compared to the adjacent control tissue. FCC(s) were determined upon direct activation of respiration with exogenously-added ADP and by titrating the complexes with their specific inhibitors to stepwise decrease their activity. MCA showed very high sensitivity of all complexes and carriers studied in human BC cells to inhibition as compared to mitochondria in normal oxidative tissues. The sum of FCC(s) for all ATP synthasome and respiratory chain components was found to be around 4, and the value exceeded significantly that for normal tissue (close to 1). In BC cells, the key sites of the regulation of respiration are Complex IV (FCC = 0.74), ATP synthase (FCC = 0.61), and phosphate carrier (FCC = 0.60); these FCC(s) exceed considerably (~10-fold) those for normal oxidative tissues. In human BC cells, the outer mitochondrial membrane is characterized by an increased permeability towards adenine nucleotides, the mean value of the apparent K(m) for ADP being equal to 114.8 ± 13.6 μM. Our data support the two-compartment hypothesis of tumor metabolism, the high sum of FCC(s) showing structural and functional organization of mitochondrial respiratory chain and ATP synthasome as supercomplexes in human BC.
Authors:
Tuuli Kaambre; Vladimir Chekulayev; Igor Shevchuk; Minna Karu-Varikmaa; Natalja Timohhina; Kersti Tepp; Jelena Bogovskaja; Riina Kütner; Vahur Valvere; Valdur Saks
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Journal of bioenergetics and biomembranes     Volume:  -     ISSN:  1573-6881     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7701859     Medline TA:  J Bioenerg Biomembr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia, tuuli.kaambre@kbfi.ee.
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