Schoepf 2016 Abstract Mito Xmas Meeting Innsbruck: Difference between revisions
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|event=Mito Xmas Meeting 2016 Innsbruck AT | |event=Mito Xmas Meeting 2016 Innsbruck AT | ||
|abstract=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. | |abstract=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. | ||
|mipnetlab=AT Innsbruck MitoFit, AT Innsbruck | |mipnetlab=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) | |||
::::# 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. | |||
{{Labeling | {{Labeling | ||
|area=Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine, Patients | |area=Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine, Patients | ||
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|preparations=Permeabilized tissue | |preparations=Permeabilized tissue | ||
|topics=Flux control | |topics=Flux control | ||
|couplingstates=LEAK, OXPHOS, | |couplingstates=LEAK, OXPHOS, ET | ||
|pathways=N, S | |pathways=N, S, Other combinations | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|event=Poster | |event=Poster | ||
|additional=Prostate cancer, Labelled by author | |additional=Prostate cancer, Labelled by author | ||
}} | }} | ||
Latest revision as of 18:39, 10 January 2022
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)
- 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
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