Schoepf 2016 Abstract Mito Xmas Meeting Innsbruck
Mitochondrial function in primary prostate cancer. |
Link:
Schoepf B, Weissensteiner H, Charoentong P, Schaefer G, Bukur V, Fendt L, Trajanoski Z, Kronenberg F, Gnaiger E, Klocker H (2016)
Event: Mito Xmas Meeting 2016 Innsbruck AT
Reprogramming of energy metabolism is a hallmark of cancer. Mutations in the mitochondrial DNA (mtDNA) might contribute to cancer development and progression. We analyzed mitochondrial respiration of fresh malignant and non-malignant prostate tissue samples obtained from 50 prostate cancer patients via High-Resolution Respirometry (HRR), determined mtDNA copy numbers by duplex qPCR, sequenced the whole mtDNAs using Next-Generation Sequencing (NGS) and analyzed expression of mitochondria-related genes in a subset of 16 cases by RNA-sequencing. HRR uncovered a shift of respiratory activity from mitochondrial complex I to complex II accompanied by a substrate shift toward higher respiratory activity elicited especially by succinate and pyruvate. The mutation load was significantly higher in tumor tissue compared to the non-malignant counterpart. Heteroplasmy levels of potentially deleterious mutations in mtDNA genes correlated significantly with reduced complex I respiration capacity. RNA-seq revealed a signature of differentially expressed metabolic enzymes in tumors exhibiting a severe compared to a mild complex CI mt-phenotype. The gene signature corresponded to observed altered substrates effects on respiration, e.g. increased pyruvate and citrate and decreased glutamate oxidation.
β’ O2k-Network Lab: AT Innsbruck MitoFit, AT Innsbruck SBI, AT Innsbruck Gnaiger E, AT Innsbruck OROBOROS
Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine, Patients Pathology: Cancer Stress:Mitochondrial disease Organism: Human
Preparation: Permeabilized tissue
Regulation: Flux control Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. Pathway: N, S HRR: Oxygraph-2k Event: Poster Prostate cancer, Labelled by author
Affiliations
- Schoepf B(1), Weissensteiner H(1), Charoentong P(2), Schaefer G(3,4), Bukur V(5), Fendt L(1), Trajanoski Z(2), Kronenberg F(1), Gnaiger E(6), Klocker H(3)
- Div Genetic Epidemiology, Dept Medical Genetics, Molecular Clinical Pharmacology
- Div Bioinformatics, Biocenter
- Div Experimental Urology, Dept Urology
- Dept Pathology
- TRON gGmbH-Translational Oncology, Johannes-Gutenberg-Univ Medical Center, Mainz, Germany
- Dept General Transplant Surgery, D. Swarovski Research Lab, Medical Univ Innsbruck, Austria.