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 Olsinova; Linda 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

doi:10.1016/j.cmet.2018.10.014

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 Olsinova

Linda 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 journal › Article › Academic › peer-review

248 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 language	English
Pages (from-to)	399-416.e10
Journal	Cell Metabolism
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2018.10.014
Publication status	Published - 5 Feb 2019
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cancer
coenzyme Q
dihydroorotate dehydrogenase
mitochondria
OXPHOS
pyrimidine biosynthesis
respiration

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10.1016/j.cmet.2018.10.014Licence: Publisher

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Bajzikova, M., Kovarova, J., Coelho, A. R., 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. J., Magalhaes Novais, S., ... Neuzil, J. (2019). Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells. Cell Metabolism, 29(2), 399-416.e10. https://doi.org/10.1016/j.cmet.2018.10.014

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title = "Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells",

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.",

keywords = "cancer, coenzyme Q, dihydroorotate dehydrogenase, mitochondria, OXPHOS, pyrimidine biosynthesis, respiration",

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

year = "2019",

month = feb,

day = "5",

doi = "10.1016/j.cmet.2018.10.014",

language = "English",

volume = "29",

pages = "399--416.e10",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Elsevier",

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}

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 Metabolism, vol. 29, no. 2, pp. 399-416.e10. https://doi.org/10.1016/j.cmet.2018.10.014

TY - JOUR

T1 - Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

AU - Bajzikova, Martina

AU - Kovarova, Jaromira

AU - Coelho, Ana R.

AU - Boukalova, Stepana

AU - Oh, Sehyun

AU - Rohlenova, Katerina

AU - Svec, David

AU - Hubackova, Sona

AU - Endaya, Berwini

AU - Judasova, Kristyna

AU - Bezawork-Geleta, Ayenachew

AU - Kluckova, Katarina

AU - Chatre, Laurent

AU - Zobalova, Renata

AU - Novakova, Anna

AU - Vanova, Katerina

AU - Ezrova, Zuzana

AU - Maghzal, Ghassan J.

AU - Magalhaes Novais, Silvia

AU - Olsinova, Marie

AU - Krobova, Linda

AU - An, Yong Jin

AU - Davidova, Eliska

AU - Nahacka, Zuzana

AU - Sobol, Margarita

AU - Cunha-Oliveira, Teresa

AU - Sandoval-Acuña, Cristian

AU - Strnad, Hynek

AU - Zhang, Tongchuan

AU - Huynh, Thanh

AU - Serafim, Teresa L.

AU - Hozak, Pavel

AU - Sardao, Vilma A.

AU - Koopman, Werner J.H.

AU - Ricchetti, Miria

AU - Oliveira, Paulo J.

AU - Kolar, Frantisek

AU - Kubista, Mikael

AU - Truksa, Jaroslav

AU - Dvorakova-Hortova, Katerina

AU - Pacak, Karel

AU - Gurlich, Robert

AU - Stocker, Roland

AU - Zhou, Yaoqi

AU - Berridge, Michael V.

AU - Park, Sunghyouk

AU - Dong, Lanfeng

AU - Rohlena, Jakub

AU - Neuzil, Jiri

PY - 2019/2/5

Y1 - 2019/2/5

N2 - 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.

AB - 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.

KW - cancer

KW - coenzyme Q

KW - dihydroorotate dehydrogenase

KW - mitochondria

KW - OXPHOS

KW - pyrimidine biosynthesis

KW - respiration

U2 - 10.1016/j.cmet.2018.10.014

DO - 10.1016/j.cmet.2018.10.014

M3 - Article

C2 - 30449682

AN - SCOPUS:85060704969

SN - 1550-4131

VL - 29

SP - 399-416.e10

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

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

Abstract

UN SDGs

Keywords

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