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Altered metabolism and mitochondrial genome in prostate cancer

¹ Genesis Genomics Inc, 1294 Balmoral Street, Thunder Bay, Ontario, Canada, P7B 5Z5
² Department of Biomedical Sciences, Dental School, University of Maryland, Baltimore, Maryland 21201, USA

Correspondence to:
Dr G D Dakubo
Genesis Genomics Inc, 1294 Balmoral Street, Thunder Bay, Ontario, Canada, P7B 5Z5; gabriel.dakubo{at}genesisgenomics.com
ABSTRACT
Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal, tumour pathogenesis. The metabolism of human prostate peripheral zone glandular epithelial cells is unique. Compared with many other soft tissues, these glandular epithelial cells accumulate high concentrations of zinc, which inhibits the activity of m-aconitase, an enzyme involved in citrate metabolism through Krebs cycle. This causes Krebs cycle truncation and accumulation of high concentrations of citrate to be secreted in prostatic fluid. The accumulation of zinc also inhibits terminal oxidation. Therefore, these cells exhibit inefficient energy production. In contrast, malignant transformation of the prostate is associated with an early metabolic switch, leading to decreased zinc accumulation and increased citrate oxidation. The efficient energy production in these transformed cells implies increased electron transport chain activity, increased oxygen consumption, and perhaps, excess reactive oxygen species (ROS) production compared with normal prostate epithelial cells. Because ROS have deleterious effects on DNA, proteins, and lipids, the altered intermediary metabolism may be linked with ROS production and accelerated mitochondrial DNA mutations in prostate cancer.

Abbreviations: HIF1, hypoxia inducible factor1; LCM, laser capture microdissection; mtDNA, mitochondrial DNA; np, nucleotides; PIN, prostate intraepithelial neoplasia; ROS, reactive oxygen species

Keywords: citrate metabolism; mitochondrial DNA; mutations; prostate cancer

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