Targeting mitochondrial oxphos and their regulatory signals in prostate cancers

Research output: Contribution to journalArticlepeer-review

Abstract

Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the increasing energy demand for rapid cellular expansion and to cope with the often nu¬tritional and oxygen-deprived microenvironment. One well-recognized strategy is to shift the met¬abolic flow from oxidative phosphorylation (OXPHOS) or respiration in mitochondria to glycolysis or fermentation in cytosol, known as Warburg effects. However, not all cancer cells follow this par¬adigm. In the development of prostate cancer, OXPHOS actually increases as compared to normal prostate tissue. This is because normal prostate epithelial cells divert citrate in mitochondria for the TCA cycle to the cytosol for secretion into seminal fluid. The sustained level of OXPHOS in primary tumors persists in progression to an advanced stage. As such, targeting OXPHOS and mitochondrial activities in general present therapeutic opportunities. In this review, we summarize the recent find¬ings of the key regulators of the OXPHOS pathway in prostate cancer, ranging from transcriptional regulation, metabolic regulation to genetic regulation. Moreover, we provided a comprehensive update of the current status of OXPHOS inhibitors for prostate cancer therapy. A challenge of de¬veloping OXPHOS inhibitors is to selectively target cancer mitochondria and spare normal coun¬terparts, which is also discussed.

Original languageEnglish
Article number13435
JournalInternational journal of molecular sciences
Volume22
Issue number24
DOIs
Publication statusPublished - Dec 1 2021

Keywords

  • Cancer therapy
  • Mitochondria
  • OXPHOS

ASJC Scopus subject areas

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

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