
DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth
- Author
- Jonathan Barra, Isaiah Crosbourne, Cassandra L. Roberge, Ramon Bossardi-Ramos, Janine S. A. Warren, Kailie Matteson, Ling Wang, Frances Jourd’heuil, Sergey M. Borisov, Erin Bresnahan, Jose Javier Bravo-Cordero, Ruslan Dmitriev (UGent) , David Jourd’heuil, Alejandro P. Adam, John M. Lamar, David T. Corr and Margarida M. Barroso
- Organization
- Abstract
- Transient early endosome (EE)-mitochondria interactions can mediate mitochondrial iron translocation, but the associated mechanisms are still elusive. We showed that Divalent Metal Transporter 1 (DMT1) sustains mitochondrial iron translocation via EE-mitochondria interactions in triple-negative MDA-MB-231, but not in luminal A T47D breast cancer cells. DMT1 silencing increases labile iron pool (LIP) levels and activates PINK1/Parkin-dependent mitophagy in MDA-MB-231 cells. Mitochondrial bioenergetics and the iron-associated protein profile were altered by DMT1 silencing and rescued by DMT1 re-expression. Transcriptomic profiles upon DMT1 silencing are strikingly different between 2D and 3D culture conditions, suggesting that the environment context is crucial for the DMT1 knockout phenotype observed in MDA-MB-231 cells. Lastly, in vivo lung metastasis assay revealed that DMT1 silencing promoted the outgrowth of lung metastatic nodules in both human and murine models of triple-negative breast cancer cells. These findings reveal a DMT1-dependent pathway connecting EE-mitochondria interactions to mitochondrial iron translocation and metastatic fitness of breast cancer cells.
- Keywords
- Cancer Research, Genetics, Molecular Biology
Downloads
-
s41388-023-02933-x.pdf
- full text (Published version)
- |
- open access
- |
- |
- 6.68 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HKN9194NFMPXMEWR0QZV2TBV
- MLA
- Barra, Jonathan, et al. “DMT1-Dependent Endosome-Mitochondria Interactions Regulate Mitochondrial Iron Translocation and Metastatic Outgrowth.” ONCOGENE, Springer Science and Business Media LLC, 2024, doi:10.1038/s41388-023-02933-x.
- APA
- Barra, J., Crosbourne, I., Roberge, C. L., Bossardi-Ramos, R., Warren, J. S. A., Matteson, K., … Barroso, M. M. (2024). DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth. ONCOGENE. https://doi.org/10.1038/s41388-023-02933-x
- Chicago author-date
- Barra, Jonathan, Isaiah Crosbourne, Cassandra L. Roberge, Ramon Bossardi-Ramos, Janine S. A. Warren, Kailie Matteson, Ling Wang, et al. 2024. “DMT1-Dependent Endosome-Mitochondria Interactions Regulate Mitochondrial Iron Translocation and Metastatic Outgrowth.” ONCOGENE. https://doi.org/10.1038/s41388-023-02933-x.
- Chicago author-date (all authors)
- Barra, Jonathan, Isaiah Crosbourne, Cassandra L. Roberge, Ramon Bossardi-Ramos, Janine S. A. Warren, Kailie Matteson, Ling Wang, Frances Jourd’heuil, Sergey M. Borisov, Erin Bresnahan, Jose Javier Bravo-Cordero, Ruslan Dmitriev, David Jourd’heuil, Alejandro P. Adam, John M. Lamar, David T. Corr, and Margarida M. Barroso. 2024. “DMT1-Dependent Endosome-Mitochondria Interactions Regulate Mitochondrial Iron Translocation and Metastatic Outgrowth.” ONCOGENE. doi:10.1038/s41388-023-02933-x.
- Vancouver
- 1.Barra J, Crosbourne I, Roberge CL, Bossardi-Ramos R, Warren JSA, Matteson K, et al. DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth. ONCOGENE. 2024;
- IEEE
- [1]J. Barra et al., “DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth,” ONCOGENE, 2024.
@article{01HKN9194NFMPXMEWR0QZV2TBV, abstract = {{Transient early endosome (EE)-mitochondria interactions can mediate mitochondrial iron translocation, but the associated mechanisms are still elusive. We showed that Divalent Metal Transporter 1 (DMT1) sustains mitochondrial iron translocation via EE-mitochondria interactions in triple-negative MDA-MB-231, but not in luminal A T47D breast cancer cells. DMT1 silencing increases labile iron pool (LIP) levels and activates PINK1/Parkin-dependent mitophagy in MDA-MB-231 cells. Mitochondrial bioenergetics and the iron-associated protein profile were altered by DMT1 silencing and rescued by DMT1 re-expression. Transcriptomic profiles upon DMT1 silencing are strikingly different between 2D and 3D culture conditions, suggesting that the environment context is crucial for the DMT1 knockout phenotype observed in MDA-MB-231 cells. Lastly, in vivo lung metastasis assay revealed that DMT1 silencing promoted the outgrowth of lung metastatic nodules in both human and murine models of triple-negative breast cancer cells. These findings reveal a DMT1-dependent pathway connecting EE-mitochondria interactions to mitochondrial iron translocation and metastatic fitness of breast cancer cells.}}, author = {{Barra, Jonathan and Crosbourne, Isaiah and Roberge, Cassandra L. and Bossardi-Ramos, Ramon and Warren, Janine S. A. and Matteson, Kailie and Wang, Ling and Jourd’heuil, Frances and Borisov, Sergey M. and Bresnahan, Erin and Bravo-Cordero, Jose Javier and Dmitriev, Ruslan and Jourd’heuil, David and Adam, Alejandro P. and Lamar, John M. and Corr, David T. and Barroso, Margarida M.}}, issn = {{0950-9232}}, journal = {{ONCOGENE}}, keywords = {{Cancer Research,Genetics,Molecular Biology}}, language = {{eng}}, pages = {{18}}, publisher = {{Springer Science and Business Media LLC}}, title = {{DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth}}, url = {{http://doi.org/10.1038/s41388-023-02933-x}}, year = {{2024}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: