Koit 2017 Oxid Med Cell Longev
|Koit A, Shevchuk I, Ounpuu L, Klepinin A, Chekulayev V, Timohhina N, Tepp K, Puurand M,Truu L, Heck K, Valvere V, Guzun R, Kaambre T (2017) Mitochondrial respiration in human colorectal and breast cancer clinical material is regulated differently. Oxid Med Cell Longev 2017:1372640.|
Abstract: We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures.
• Keywords: Mitochondria, Human breast cancer, Human colorectal cancer, Respiratory chain, Metabolic control analysis, Mitochondrial supercomplexes • Bioblast editor: Kandolf G • O2k-Network Lab: EE Tallinn Kaambre T, EE Tallinn Saks VA
Labels: MiParea: Respiration, mt-Membrane, Patients Pathology: Cancer
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Supercomplex Regulation: ADP Coupling state: LEAK, OXPHOS Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k