OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation.

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 incre

SUBMITTER: Schopf B 

PROVIDER: S-EPMC7083862 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature