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

https://doi.org/10.1016/j.cmet.2018.10.014

Bajzikova M, Kovarova J, Coelho AR, Boukalova S, Oh S, Rohlenova K, Svec D, Hubackova S, Endaya B, Judasova K, Bezawork-Geleta A, Kluckova K, Chatre L, Zobalova R, Novakova A, Vanova K, Ezrova Z, Maghzal GJ, Magalhaes Novais S, Olsinova M, Krobova L, An YJ, Davidova E, Nahacka Z, Sobol M, Cunha-Oliveira T, Sandoval-Acuña C, Strnad H, Zhang T, Huynh T, Serafim TL, Hozak P, Sardao VA, Koopman WJH, Ricchetti M, Oliveira PJ, Kolar F, Kubista M, Truksa J, Dvorakova-Hortova K, Pacak K, Gurlich R, Stocker R, Zhou Y, Berridge MV, Park S, Dong L, Rohlena J, Neuzil J.

• The authors graft cancer cells lacking mtDNA (ρ⁰) onto mice, and show horizontal transfer of mtDNA into the cancer cells after a lag period. After the transfer of mtDNA, a tumour subsequently develops. 
• The authors show that OXPHOS-derived ATP is not essential for tumorigenesis 
• Pyrimidine biosynthesis is dependent on respiration, and is required for cell-cycle progression