Schoepf 2020 Nat Commun

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Schöpf Bernd, Weissensteiner Hansi, Schäfer Georg, Fazzini Federica, Charoentong Pornpimol, Naschberger Andreas, Rupp Bernhard, Fendt Liane, Bukur Valesca, Giese Irina, Sorn Patrick, Sant’Anna-Silva Ana Carolina, Iglesias-Gonzalez Javier, Sahin Ugur, Kronenberg Florian, Gnaiger Erich, Klocker Helmut (2020) OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation. Nat Commun 11:1487.

» Open Access »O2k-brief

Schoepf Bernd, Weissensteiner Hansi, Schaefer Georg, Fazzini Federica, Charoentong Pornpimol, Naschberger Andreas, Rupp Bernhard, Fendt Liane, Bukur Valesca, Giese Irina, Sorn Patrick, Sant’Anna-Silva Ana Carolina, Iglesias-Gonzalez Javier, Sahin Ugur, Kronenberg Florian, Gnaiger Erich, Klocker Helmut (2020) Nat Commun

Abstract: Rewiring of energy metabolism and adaptation of mitochondria are considered to impact on prostate cancer development and progression. Here we report on mitochondrial respiration, DNA mutations and gene expression in paired benign/malignant human prostate tissue samples. Results reveal reduced respiratory capacities with NADH-pathway substrates glutamate and malate in malignant tissue and a significant metabolic shift towards higher succinate oxidation, particularly in high-grade tumors. The load of potentially deleterious mitochondrial-DNA mutations is higher in tumors and associated with unfavorable risk factors. High levels of potentially deleterious mutations in mitochondrial Complex I-encoding genes are associated with a 70% reduction in NADH-pathway capacity and compensation by increased succinate-pathway capacity. Structural analyses of these mutations reveal amino acid alterations leading to potentially deleterious effects on Complex I, supporting a causal relationship. A metagene signature extracted from the transcriptome of tumor samples exhibiting a severe mitochondrial phenotype enables identification of tumors with shorter survival times.


Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros


Labels: MiParea: Respiration, mtDNA;mt-genetics, mt-Medicine, Patients  Pathology: Cancer 

Organism: Human  Tissue;cell: Genital, Other cell lines  Preparation: Permeabilized cells, Permeabilized tissue  Enzyme: Complex I  Regulation: Coupling efficiency;uncoupling, Flux control, Inhibitor  Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k 

Alert2020, O2k-brief 

MitoFit Preprint