2. Academic Validation
  3. Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer

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.
Stepana Boukalova 1,  Sona Hubackova 1,  Mirko Milosevic 1,  Zuzana Ezrova 2,  Jiri Neuzil 3,  Jakub Rohlena 4
Affiliations

Affiliations

  • 1 Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, 252 50 Vestec, Prague-West, Czech Republic.
  • 2 Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, 252 50 Vestec, Prague-West, Czech Republic; Faculty of Science, Charles University, Prague, Czech Republic.
  • 3 Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, 252 50 Vestec, Prague-West, Czech Republic; School of Medical Science, Griffith University, Southport, 4222, Qld, Australia.
  • 4 Institute of Biotechnology, Czech Academy of Sciences, BIOCEV, 252 50 Vestec, Prague-West, Czech Republic. Electronic address: jakub.rohlena@ibt.cas.cz.
PMID: 32151633 DOI: 10.1016/j.bbadis.2020.165759
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.

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