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.

• 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)

1. Div Genetic Epidemiology, Dept Medical Genetics, Molecular Clinical Pharmacology
2. Div Bioinformatics, Biocenter
3. Div Experimental Urology, Dept Urology
4. Dept Pathology
5. TRON gGmbH-Translational Oncology, Johannes-Gutenberg-Univ Medical Center, Mainz, Germany
6. Dept General Transplant Surgery, D. Swarovski Research Lab, Medical Univ Innsbruck, Austria.