Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer

Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165759. doi: 10.1016/j.bbadis.2020.165759. Epub 2020 Mar 6.

Abstract

Dihydroorotate dehydrogenase (DHODH) is an enzyme of the de novo pyrimidine synthesis pathway that provides nucleotides for RNA/DNA synthesis essential for proliferation. In mammalian cells, DHODH is localized in mitochondria, linked to the respiratory chain via the coenzyme Q pool. Here we discuss the role of DHODH in the oxidative phosphorylation system and in the initiation and progression of cancer. We summarize recent findings on DHODH biology, the progress made in the development of new, specific inhibitors of DHODH intended for cancer therapy, and the mechanistic insights into the consequences of DHODH inhibition.

Keywords: Bioenergetics; Cancer; De novo pyrimidine synthesis; Dehydroorotate dehydrogenase; Oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Proliferation / drug effects
  • Dihydroorotate Dehydrogenase
  • Electron Transport / genetics
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Oxidative Phosphorylation*
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors
  • Oxidoreductases Acting on CH-CH Group Donors / genetics*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / genetics

Substances

  • Dihydroorotate Dehydrogenase
  • Enzyme Inhibitors
  • Ubiquinone
  • Oxidoreductases Acting on CH-CH Group Donors
  • coenzyme Q10