Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer.

Authors :: Boukalova S
Hubackova S
Milosevic M
Ezrova Z
Neuzil J
Rohlena J
Source :: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2020 Jun 01; Vol. 1866 (6), pp. 165759. Date of Electronic Publication: 2020 Mar 06.
Publication Year :: 2020
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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)