The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Mitochondrial RNA modifications shape metabolic plasticity in metastasis
Open accessAbstract
Aggressive and metastatic cancers show enhanced metabolic plasticity 1, but the precise underlying mechanisms of this remain unclear. Here we show how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent RNA modifications—5-methylcytosine (m 5 C) and its derivative 5-formylcytosine (f 5 C) (refs.2–4)—drive the translation of mitochondrial mRNA to power metastasis. Translation of mitochondrially encoded subunits of the oxidative phosphorylation complex depends on the formation of m 5 C at position 34 in mitochondrial tRNA Met. m 5 C-deficient human oral cancer cells exhibit increased levels of glycolysis and changes in their mitochondrial function that do not affect cell viability or primary tumour growth in vivo; however, metabolic plasticity is severely impaired as mitochondrial m 5 C-deficient tumours do not metastasize efficiently. We discovered that CD36-dependent non-dividing, metastasis-initiating tumour cells require mitochondrial m 5 C to activate invasion and dissemination. Moreover, a mitochondria-driven gene signature in patients with head and neck cancer is predictive for metastasis and disease progression. Finally, we confirm that this metabolic switch that allows the metastasis of tumour cells can be pharmacologically targeted through the inhibition of mitochondrial mRNA translation in vivo. Together, our results reveal that site-specific mitochondrial RNA modifications could be therapeutic targets to combat metastasis.
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Cites
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Cited by
Gerstberger, S., Jiang, Q., & Ganesh, K. (2023) · Cell · doi:10.1016/j.cell.2023.03.003 · Cited by 913
Tumor glycolysis, an essential sweet tooth of tumor cells
Paul, S., Ghosh, S., & Kumar, S. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.09.007 · Cited by 449
Mitochondria: It is all about energy
Casanova, A., Wevers, A., Navarro-Ledesma, S., & Pruimboom, L. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1114231 · Cited by 303
The mitochondrial methylation potential gates mitoribosome assembly
Glasgow, R. I. C., Singh, V., Peña-Pérez, L., Wilhalm, A., Moedas, M. F., Moore, D., Rosenberger, F. A., Li, X., Atanassov, I., Saba, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60977-x · Cited by 14
Metadata
- Authors
- Delaunay, S., Pascual, G., Feng, B., Klann, K., Behm, M., Hotz-Wagenblatt, A., Richter, K., Zaoui, K., Herpel, E., Münch, C., Dietmann, S., Hess, J., Benitah, S. A., & Frye, M.
- Venue
- Nature
- Published
- 2022-06-29
- Volume
- 607
- Issue
- 7919
- Pages
- 593-603
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W4283744632
- Cited by
- 303
- References
- 54
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Delaunay, S., Pascual, G., Feng, B., Klann, K., Behm, M., Hotz-Wagenblatt, A., Richter, K., Zaoui, K., Herpel, E., Münch, C., Dietmann, S., Hess, J., Benitah, S. A., & Frye, M. (2022). Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature. https://doi.org/10.1038/s41586-022-04898-5
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