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 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.

• O2k-Network Lab: AT Innsbruck MitoFit, AT Innsbruck Oroboros

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; Oroboros Instruments, Austria.

Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine, Patients  Pathology: Cancer 

Organism: Human 

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