Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa.
Original languageEnglish (US)
Article number12168
Pages (from-to)12168
JournalInternational journal of molecular sciences
Volume23
Issue number20
DOIs
StatePublished - Oct 12 2022

Keywords

  • TCA cycle
  • citrate
  • electron transport system
  • respiratory analysis
  • Reactive Oxygen Species/metabolism
  • Electron Transport
  • Electron Transport Complex I/metabolism
  • Citrates
  • Humans
  • Male
  • Succinic Acid/metabolism
  • Prostatic Neoplasms
  • Electron Transport Complex II/metabolism
  • Ubiquinone/metabolism
  • NAD/metabolism
  • Zinc/metabolism

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Enhanced Succinate Oxidation with Mitochondrial Complex II Reactive Oxygen Species Generation in Human Prostate Cancer'. Together they form a unique fingerprint.

Cite this