Schoepf 2019 MitoFit Preprint Arch

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Gnaiger 2019 MitoFit Preprints
Gnaiger MitoFit Preprints 2020.4
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Schoepf 2019 MitoFit Preprint Arch

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Schรถpf B, Weissensteiner H, Schรคfer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, Eichelbrรถnner 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. - 2020-03-20 published in ยปNature Communications 11:1487ยซ

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OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and a prognostic gene expression signature

MitoFit Prep 2019.3. (2019) MitoFit Prep

Abstract: Version 1 (v1) 2019-06-11 doi:10.26124/mitofit:190003 - 2020-03-20 Published in ยปNature Communications 11:1487ยซ

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. โ€ข Keywords: Mitochondria, high-resolution respirometry, oxidative phosphorylation, mitochondrial DNA mutation, mtDNA heteroplasmy, metabolic reprograming โ€ข Bioblast editor: Gnaiger E


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