Schoepf 2020 Nat Commun

Schöpf B, Weissensteiner H, Schäfer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, Giese I, Sorn P, Sant’Anna-Silva AC, Iglesias-Gonzalez J, Sahin U, Kronenberg F, Gnaiger E, Klocker H (2020) OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation. Nat Commun 11:1487. https://doi.org/10.1038/s41467-020-15237-5

» PMID: 32198407 Open Access »

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 Oroboros

MitoFit Preprint

• Schöpf et al (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. - »Bioblast link«

Cited by

• 22 articles in PubMed (2021-12-27) https://pubmed.ncbi.nlm.nih.gov/32198407/

Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.8. https://doi.org/10.26124/mitofit:2021-0008

Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5^th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002

Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1.

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, BEC 2020.1, BEC 2020.2, MitoFit 2021 BCA