Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation. / Desler, Claus; Durhuus, Jon Ambæk; Hansen, Thomas Lau Lindestrand; Anugula, Sharath; Zelander, Nadia Thaulov; Bøggild, Sisse; Rasmussen, Lene Juel.

In: Mitochondrion, Vol. 64, 2022, p. 73-81.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Desler, C, Durhuus, JA, Hansen, TLL, Anugula, S, Zelander, NT, Bøggild, S & Rasmussen, LJ 2022, 'Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation', Mitochondrion, vol. 64, pp. 73-81. https://doi.org/10.1016/j.mito.2022.03.005

APA

Desler, C., Durhuus, J. A., Hansen, T. L. L., Anugula, S., Zelander, N. T., Bøggild, S., & Rasmussen, L. J. (2022). Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation. Mitochondrion, 64, 73-81. https://doi.org/10.1016/j.mito.2022.03.005

Vancouver

Desler C, Durhuus JA, Hansen TLL, Anugula S, Zelander NT, Bøggild S et al. Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation. Mitochondrion. 2022;64:73-81. https://doi.org/10.1016/j.mito.2022.03.005

Author

Desler, Claus ; Durhuus, Jon Ambæk ; Hansen, Thomas Lau Lindestrand ; Anugula, Sharath ; Zelander, Nadia Thaulov ; Bøggild, Sisse ; Rasmussen, Lene Juel. / Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation. In: Mitochondrion. 2022 ; Vol. 64. pp. 73-81.

Bibtex

@article{5f4373024d334384abfdb1e7d8e25797,
title = "Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation",
abstract = "The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. The enzyme dihydroorotate dehydrogenase (DHODH) links oxidative phosphorylation to de novo synthesis of pyrimidines. We demonstrate that an inhibition of DHODH results in a respiration-independent significant increase of anchorage-independent growth but does not affect DNA repair ability. Instead, we show an autophagy-independent increase of lysosomes. The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype.",
keywords = "DNA repair, Lysosome increase, Mitochondria, Mitochondrial-linked pyrimidine synthesis, Tumorigenesis",
author = "Claus Desler and Durhuus, {Jon Amb{\ae}k} and Hansen, {Thomas Lau Lindestrand} and Sharath Anugula and Zelander, {Nadia Thaulov} and Sisse B{\o}ggild and Rasmussen, {Lene Juel}",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
doi = "10.1016/j.mito.2022.03.005",
language = "English",
volume = "64",
pages = "73--81",
journal = "Mitochondrion",
issn = "1567-7249",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation

AU - Desler, Claus

AU - Durhuus, Jon Ambæk

AU - Hansen, Thomas Lau Lindestrand

AU - Anugula, Sharath

AU - Zelander, Nadia Thaulov

AU - Bøggild, Sisse

AU - Rasmussen, Lene Juel

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. The enzyme dihydroorotate dehydrogenase (DHODH) links oxidative phosphorylation to de novo synthesis of pyrimidines. We demonstrate that an inhibition of DHODH results in a respiration-independent significant increase of anchorage-independent growth but does not affect DNA repair ability. Instead, we show an autophagy-independent increase of lysosomes. The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype.

AB - The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. The enzyme dihydroorotate dehydrogenase (DHODH) links oxidative phosphorylation to de novo synthesis of pyrimidines. We demonstrate that an inhibition of DHODH results in a respiration-independent significant increase of anchorage-independent growth but does not affect DNA repair ability. Instead, we show an autophagy-independent increase of lysosomes. The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype.

KW - DNA repair

KW - Lysosome increase

KW - Mitochondria

KW - Mitochondrial-linked pyrimidine synthesis

KW - Tumorigenesis

U2 - 10.1016/j.mito.2022.03.005

DO - 10.1016/j.mito.2022.03.005

M3 - Journal article

C2 - 35346867

AN - SCOPUS:85127076106

VL - 64

SP - 73

EP - 81

JO - Mitochondrion

JF - Mitochondrion

SN - 1567-7249

ER -

ID: 305713364