Maedo 2014 Abstract IOC 2014-04 Schroecken

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Maedo K, Kaldma A, Planken A, Klepinin A, Chekulayev V, Varikmaa M, Tepp K, Chevchuk I, Kaambre T (2014) Regulation of mitochondrial respiration in human colorectal cancer cells in situ: the possible role of beta-tubulins. Mitochondr Physiol Network 19.02.


Maedo K, Kaldma A, Planken A, Klepinin A, Chekulayev V, Varikmaa M, Tepp K, Chevchuk I, Kaambre T (2014)

Event: MiPNet19.02 IOC88

For decades it has been known that cancer cells establish a specific metabolic profile, characterized as aerobic fermentation or the Warburg effect. However, at least some cancers exhibit increased oxidative phosphorylation (OXPHOS). We have analyzed human post-operative tissue samples from colorectal adenocarcinomas compared to adjacent control colon tissue samples. Our preliminary results indicate that the colorectal adenocarcinoma is not a pure glycolytic tumor and the OXPHOS system may be the main provider of ATP in these cells. The apparent Km for ADP and Jmax values are calculated for the characterization of the affinity of mitochondria for exogenous ADP: control colon tissue displayed very low affinity for ADP (K´m ≈ 250µM) in contrast to tumor tissue, where the affinity was significantly higher (K´m ≈ 120µM). At the same time there was 1.75 times higher maximal respiration rate in tumor samples compared to controls, suggesting cancer`s enhanced respiration capacity. Changes in the value of the K´m for ADP have been previously associated with the binding of cytoskeletal tubulin to voltage dependent anion channel (VDAC) in the mitochondrial outer membrane. In cardiomyocytes VDAC is probably regulated by tubulin βII isoform. To clarify the role of tubulins in cancer and normal colon tissue samples we examined tubulin βI, βII, βIII and βIV mRNA and protein expression profiles. Our results show that tubulin βII expression levels are similar in both samples, but there is an increase in tumour`s tubulin βIII level. To conclude, in colorectal cancer other mechanisms are probably involved in the permeability of VDAC for ADP.

Keywords: Human colorectal adenocarcinoma, OXPHOS, VDAC permeability, Beta-tubulins

O2k-Network Lab: EE Tallinn Kaambre T

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Permeabilized tissue 

Regulation: ADP  Coupling state: OXPHOS 

HRR: Oxygraph-2k