Kaambre 2013 Front Physiol

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Kaambre T, Chekulayev V, Shevchuk I, Tepp K, Timohhina N, Varikmaa M, Bagur R, Klepinin A, Anmann T, Koit A, Kaldma A, Guzun R, Valvere V, Saks V (2013) Metabolic control analysis of respiration in human cancer tissue. Front Physiol 4:151.

» PMID:23825460 Open Access

Kaambre T, Chekulayev V, Shevchuk I, Tepp K, Timohhina N, Varikmaa M, Bagur R, Klepinin A, Anmann T, Koit A, Kaldma A, Guzun R, Valvere V, Saks V (2013) Front Physiol

Abstract: Bioenergetic profiling of cancer cells is of great potential because it can bring forward new and effective therapeutic strategies along with early diagnosis. Metabolic Control Analysis (MCA) is a methodology that enables quantification of the flux control exerted by different enzymatic steps in a metabolic network thus assessing their contribution to the system's function. Our main goal is to demonstrate the applicability of MCA for in situ studies of energy metabolism in human breast and colorectal cancer cells as well as in normal tissues. We seek to determine the metabolic conditions leading to energy flux redirection in cancer cells. A main result obtained is that the adenine nucleotide translocator exhibits the highest control of respiration in human breast cancer thus becoming a prospective therapeutic target. Additionally, we present evidence suggesting the existence of mitochondrial respiratory supercomplexes that may represent a way by which cancer cells avoid apoptosis. The data obtained show that MCA applied in situ can be insightful in cancer cell energetic research.

Keywords: Metabolic control analysis, Respiratory chain, Breast and colorectal cancer, Warburg effect, OXPHOS

O2k-Network Lab: EE Tallinn Saks VA, EE Tallinn Kaambre T


Labels: MiParea: Respiration  Pathology: Cancer  Stress:Cell death  Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized tissue  Enzyme: Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex  Regulation: ADP, Flux control, Inhibitor, PCr;Cr 


HRR: Oxygraph-2k