Schoepf 2019 MitoFit Preprint Arch
SchΓΆpf B, Weissensteiner H, SchΓ€fer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, EichelbrΓΆnner 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. https://doi.org/10.26124/mitofit:190003 - 2020-03-20 published in Β»Nature Communications 11:1487Β« |
Β» MitoFit Preprint Arch 2019.3.
MitoFit Prep 2019.3. (2019) MitoFit Prep
Abstract: Version 1 (v1) 2019-06-11 doi:10.26124/mitofit:190003 - 2020-03-20 Published in Β»Nature Communications 11:1487Β«
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. β’ Keywords: Mitochondria, high-resolution respirometry, oxidative phosphorylation, mitochondrial DNA mutation, mtDNA heteroplasmy, metabolic reprograming β’ Bioblast editor: Gnaiger E
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