Schoepf 2019 MitoFit Preprint Arch

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Schoepf 2019 MitoFit Preprint Arch

Publications in the MiPMap
Schöpf B, Weissensteiner H, Schäfer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, Eichelbrönner I, Sorn P, Sahin U, Kronenberg F, Gnaiger E, Klocker H (2019) OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and a prognostic gene expression signature. MitoFit Preprint Arch doi:10.26124/mitofit:190003.
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OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and a prognostic gene expression signature


Schoepf B, Weissensteiner H, Schaefer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, Eichelbroenner I, Sorn P, Sahin U, Kronenberg F, Gnaiger E, Klocker H (2019) MitoFit Preprint Arch

Abstract: Version 1 (v1) 2019-06-11 doi:10.26124/mitofit:190003

Rewiring of energy metabolism and adaptation of mitochondrial respiratory functions are considered to impact on prostate cancer development and progression. High-resolution respirometry of paired benign and malignant human prostate tissue samples revealed reduced respiratory capacities with NADH-pathway substrates glutamate and malate in malignant tissue and a significant metabolic shift towards respiratory capacity with succinate, particularly in high-grade tumors. The load of potentially deleterious mitochondrial-DNA mutations was higher in tumor tissue and associated with unfavorable risk factors. High levels of potentially deleterious mutations in mitochondrial Complex I-encoding genes were associated with a 70% reduction in NADH-pathway capacity and compensation by increased S-pathway capacity. Structural analyses of these mutations revealed amino acid alterations leading to potentially deleterious effects on Complex I, supporting a causal relationship. RNA-seq revealed a signature of metabolic enzymes corresponding to the altered mitochondrial respiratory pathways and enabled extraction of a metagene set for prediction of shorter disease-free survival.

Keywords: Mitochondria, high-resolution respirometry, oxidative phosphorylation, mitochondrial DNA mutation, mtDNA heteroplasmy, metabolic reprograming Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Oroboros, AT Innsbruck Gnaiger E

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Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, mt-Medicine  Pathology: Cancer  Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Genital  Preparation: Permeabilized tissue  Enzyme: Complex I, TCA cycle and matrix dehydrogenases 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

MitoEAGLEPublication