Schoepf 2019 MitoFit Preprint Arch

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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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MitoFit pdf

Version 1: 2019-06-11 Open Access doi:10.26124/mitofit:190003

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: 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


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 

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