Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

Martina Bajzikova, Jaromira Kovarova*, Ana R. Coelho, Stepana Boukalova, Sehyun Oh, Katerina Rohlenova, David Svec, Sona Hubackova, Berwini Endaya, Kristyna Judasova, Ayenachew Bezawork-Geleta, Katarina Kluckova, Laurent Chatre, Renata Zobalova, Anna Novakova, Katerina Vanova, Zuzana Ezrova, Ghassan J. Maghzal, Silvia Magalhaes Novais, Marie OlsinovaLinda Krobova, Yong Jin An, Eliska Davidova, Zuzana Nahacka, Margarita Sobol, Teresa Cunha-Oliveira, Cristian Sandoval-Acuña, Hynek Strnad, Tongchuan Zhang, Thanh Huynh, Teresa L. Serafim, Pavel Hozak, Vilma A. Sardao, Werner J.H. Koopman, Miria Ricchetti, Paulo J. Oliveira, Frantisek Kolar, Mikael Kubista, Jaroslav Truksa, Katerina Dvorakova-Hortova, Karel Pacak, Robert Gurlich, Roland Stocker, Yaoqi Zhou, Michael V. Berridge, Sunghyouk Park, Lanfeng Dong, Jakub Rohlena, Jiri Neuzil

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

193 Citations (Scopus)

Abstract

Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they can highjack host mitochondria. Bajzikova et al. show that the acquired mitochondrial electron transport is necessary to drive de novo pyrimidine synthesis to overcome cell-cycle arrest. Surprisingly, ATP generation is dispensable for tumorigenesis in this context.

Original languageEnglish
Pages (from-to)399-416.e10
JournalCell Metabolism
Volume29
Issue number2
DOIs
Publication statusPublished - 5 Feb 2019
Externally publishedYes

Keywords

  • cancer
  • coenzyme Q
  • dihydroorotate dehydrogenase
  • mitochondria
  • OXPHOS
  • pyrimidine biosynthesis
  • respiration

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