Schoepf 2016 Abstract Mito Xmas Meeting Innsbruck
|Mitochondrial function in primary prostate cancer.|
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 by high-resolution respirometry (HRR), determined mtDNA copy numbers by duplex qPCR, sequenced the whole mtDNAs using next-generation sequencing (NGS) and analyzed expression of mt-related genes in a subset of 16 cases by RNA-sequencing. HRR uncovered a shift of respiratory activity from the glutamate&malate to pyruvate and succinate-pathways. 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 NADH-linked respiratory capacity. RNA-seq revealed a signature of differentially expressed metabolic enzymes in tumors exhibiting a severe compared to a mild NADH-pathway mt-phenotype. The gene signature corresponded to observed altered substrates effects on respiration, e.g. increased pyruvate and citrate and decreased glutamate oxidation.
- 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; Oroboros Instruments, Austria.
Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine, Patients Pathology: Cancer
Preparation: Permeabilized tissue
Regulation: Flux control Coupling state: LEAK, OXPHOS, ET Pathway: N, S, Other combinations HRR: Oxygraph-2k Event: Poster Prostate cancer, Labelled by author