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Bajzikova 2019 Cell Metab
Additional label 2018-11  + , PBI-Shredder  +
Coupling states OXPHOS  + , ET  +
Diseases Cancer  +
Enzyme Complex I  + , Complex II;succinate dehydrogenase  + , Complex III  + , Complex V;ATP synthase  +
Has abstract Cancer cells without mitochondrial DNA (mt
Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH in mtDNA-deficient cells is fully activated with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by introduction of an alternative oxidase. Further, deletion of DHODH interferes with tumor formation in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little effect. Our results show that DHODH-driven pyrimidine biosynthesis is an essential pathway linking respiration to tumorigenesis, pointing to inhibitors of DHODH as potential anti-cancer agents.
of DHODH as potential anti-cancer agents.  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/30449682 PMID: 30449682]  +
Has publicationkeywords OXPHOS  + , Cancer  + , Coenzyme Q  + , Dihydroorotate dehydrogenase  + , Mitochondria  + , Pyrimidine biosynthesis  + , Respiration  +
Has title Bajzikova M, Kovarova J, Coelho AR, Boukal
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 (2019) Reactivation of dihydroorotate dehydrogenase-driven pyrimidine biosynthesis restores tumor growth of respiration-deficient cancer cells. Cell Metab 29:399-416.
cient cancer cells. Cell Metab 29:399-416.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Genetic knockout;overexpression  +
Pathways N  + , S  + , ROX  +
Preparation Permeabilized cells  + , Homogenate  +
Tissue and cell Endothelial;epithelial;mesothelial cell  + , Genital  + , Other cell lines  +
Was published by MiPNetLab CZ Prague Neuzil J + , NL Nijmegen Koopman WJH + , AU Sydney Stocker R + , AU Queensland Peart J + , AU Queensland Neuzil J +
Was published in journal Cell Metab +
Was published in year 2019  +
Was written by 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 G + , Magalhaes Novais S + , Olsinova M + , Krobova L + , An YJ + , Davidova E + , Nahacka Z + , Sobol M + , Cunha-Oliveira T + , Sandoval-Acuna 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 +
Categories Publications
Modification date
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11:46:38, 9 August 2019  +
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