IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51847-z.html
   My bibliography  Save this article

Nuclear localization of MTHFD2 is required for correct mitosis progression

Author

Listed:
  • Natalia Pardo-Lorente

    (Dr. Aiguader 88)

  • Anestis Gkanogiannis

    (Dr. Aiguader 88)

  • Luca Cozzuto

    (Dr. Aiguader 88)

  • Antoni Gañez Zapater

    (Dr. Aiguader 88)

  • Lorena Espinar

    (Dr. Aiguader 88)

  • Ritobrata Ghose

    (Dr. Aiguader 88)

  • Jacqueline Severino

    (Dr. Aiguader 88)

  • Laura García-López

    (Dr. Aiguader 88)

  • Rabia Gül Aydin

    (Dr. Aiguader 88)

  • Laura Martin

    (Dr. Aiguader 88)

  • Maria Victoria Neguembor

    (Dr. Aiguader 88)

  • Evangelia Darai

    (Dr. Aiguader 88)

  • Maria Pia Cosma

    (Dr. Aiguader 88
    Universitat Pompeu Fabra (UPF))

  • Laura Batlle-Morera

    (Dr. Aiguader 88
    Universitat Pompeu Fabra (UPF))

  • Julia Ponomarenko

    (Dr. Aiguader 88
    Universitat Pompeu Fabra (UPF))

  • Sara Sdelci

    (Dr. Aiguader 88
    Universitat Pompeu Fabra (UPF))

Abstract

Subcellular compartmentalization of metabolic enzymes establishes a unique metabolic environment that elicits specific cellular functions. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we show that the nuclear localization of the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces severe methylation defects and impedes correct mitosis completion. MTHFD2 deficient cells display chromosome congression and segregation defects and accumulate chromosomal aberrations. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, whereas restricting MTHFD2 to the nucleus is sufficient to ensure correct mitotic progression. Our discovery uncovers a nuclear role for MTHFD2, supporting the notion that translocation of metabolic enzymes to the nucleus is required to meet precise chromatin needs.

Suggested Citation

  • Natalia Pardo-Lorente & Anestis Gkanogiannis & Luca Cozzuto & Antoni Gañez Zapater & Lorena Espinar & Ritobrata Ghose & Jacqueline Severino & Laura García-López & Rabia Gül Aydin & Laura Martin & Mari, 2024. "Nuclear localization of MTHFD2 is required for correct mitosis progression," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51847-z
    DOI: 10.1038/s41467-024-51847-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51847-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51847-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. V. Barra & D. Fachinetti, 2018. "The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    2. Antonio Tedeschi & Gordana Wutz & Sébastien Huet & Markus Jaritz & Annelie Wuensche & Erika Schirghuber & Iain Finley Davidson & Wen Tang & David A. Cisneros & Venugopal Bhaskara & Tomoko Nishiyama & , 2013. "Wapl is an essential regulator of chromatin structure and chromosome segregation," Nature, Nature, vol. 501(7468), pages 564-568, September.
    3. Roland Nilsson & Mohit Jain & Nikhil Madhusudhan & Nina Gustafsson Sheppard & Laura Strittmatter & Caroline Kampf & Jenny Huang & Anna Asplund & Vamsi K. Mootha, 2014. "Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    4. Yasuhiro Arimura & Hiroaki Tachiwana & Hiroki Takagi & Tetsuya Hori & Hiroshi Kimura & Tatsuo Fukagawa & Hitoshi Kurumizaka, 2019. "The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    5. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    6. Kuhn, Max, 2008. "Building Predictive Models in R Using the caret Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 28(i05).
    7. Wei Li & Qi Long & Hao Wu & Yanshuang Zhou & Lifan Duan & Hao Yuan & Yingzhe Ding & Yile Huang & Yi Wu & Jinyu Huang & Delong Liu & Baodan Chen & Jian Zhang & Juntao Qi & Shiwei Du & Linpeng Li & Yang, 2022. "Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Yael Cohen-Sharir & James M. McFarland & Mai Abdusamad & Carolyn Marquis & Sara V. Bernhard & Mariya Kazachkova & Helen Tang & Marica R. Ippolito & Kathrin Laue & Johanna Zerbib & Heidi L. H. Malaby &, 2021. "Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition," Nature, Nature, vol. 590(7846), pages 486-491, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Johanna Zerbib & Marica Rosaria Ippolito & Yonatan Eliezer & Giuseppina Feudis & Eli Reuveni & Anouk Savir Kadmon & Sara Martin & Sonia Viganò & Gil Leor & James Berstler & Julia Muenzner & Michael Mü, 2024. "Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Lorenza Garribba & Giuseppina De Feudis & Valentino Martis & Martina Galli & Marie Dumont & Yonatan Eliezer & René Wardenaar & Marica Rosaria Ippolito & Divya Ramalingam Iyer & Andréa E. Tijhuis & Dia, 2023. "Short-term molecular consequences of chromosome mis-segregation for genome stability," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Prabal Das & D. A. Sachindra & Kironmala Chanda, 2022. "Machine Learning-Based Rainfall Forecasting with Multiple Non-Linear Feature Selection Algorithms," Water Resources Management: An International Journal, Published for the European Water Resources Association (EWRA), Springer;European Water Resources Association (EWRA), vol. 36(15), pages 6043-6071, December.
    5. Jie Zhao & Ji Chen & Damien Beillouin & Hans Lambers & Yadong Yang & Pete Smith & Zhaohai Zeng & Jørgen E. Olesen & Huadong Zang, 2022. "Global systematic review with meta-analysis reveals yield advantage of legume-based rotations and its drivers," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    6. Piaopiao Chen & Agnès H. Michel & Jianzhi Zhang, 2022. "Transposon insertional mutagenesis of diverse yeast strains suggests coordinated gene essentiality polymorphisms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Paulo Infante & Gonçalo Jacinto & Anabela Afonso & Leonor Rego & Pedro Nogueira & Marcelo Silva & Vitor Nogueira & José Saias & Paulo Quaresma & Daniel Santos & Patrícia Góis & Paulo Rebelo Manuel, 2023. "Factors That Influence the Type of Road Traffic Accidents: A Case Study in a District of Portugal," Sustainability, MDPI, vol. 15(3), pages 1-16, January.
    8. Ephrem Habyarimana & Faheem S Baloch, 2021. "Machine learning models based on remote and proximal sensing as potential methods for in-season biomass yields prediction in commercial sorghum fields," PLOS ONE, Public Library of Science, vol. 16(3), pages 1-23, March.
    9. Banks, Jonathan & Rabbani, Arif & Nadkarni, Kabir & Renaud, Evan, 2020. "Estimating parasitic loads related to brine production from a hot sedimentary aquifer geothermal project: A case study from the Clarke Lake gas field, British Columbia," Renewable Energy, Elsevier, vol. 153(C), pages 539-552.
    10. Crespo, Cristian, 2020. "Two become one: improving the targeting of conditional cash transfers with a predictive model of school dropout," LSE Research Online Documents on Economics 123139, London School of Economics and Political Science, LSE Library.
    11. Alexander Wettstein & Gabriel Jenni & Ida Schneider & Fabienne Kühne & Martin grosse Holtforth & Roberto La Marca, 2023. "Predictors of Psychological Strain and Allostatic Load in Teachers: Examining the Long-Term Effects of Biopsychosocial Risk and Protective Factors Using a LASSO Regression Approach," IJERPH, MDPI, vol. 20(10), pages 1-20, May.
    12. Tang, Kayu & Parsons, David J. & Jude, Simon, 2019. "Comparison of automatic and guided learning for Bayesian networks to analyse pipe failures in the water distribution system," Reliability Engineering and System Safety, Elsevier, vol. 186(C), pages 24-36.
    13. Daifeng Xiang & Gangsheng Wang & Jing Tian & Wanyu Li, 2023. "Global patterns and edaphic-climatic controls of soil carbon decomposition kinetics predicted from incubation experiments," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Joel Podgorski & Oliver Kracht & Luis Araguas-Araguas & Stefan Terzer-Wassmuth & Jodie Miller & Ralf Straub & Rolf Kipfer & Michael Berg, 2024. "Groundwater vulnerability to pollution in Africa’s Sahel region," Nature Sustainability, Nature, vol. 7(5), pages 558-567, May.
    15. Bellotti, Anthony & Brigo, Damiano & Gambetti, Paolo & Vrins, Frédéric, 2021. "Forecasting recovery rates on non-performing loans with machine learning," International Journal of Forecasting, Elsevier, vol. 37(1), pages 428-444.
    16. Tranos, Emmanouil & Incera, Andre Carrascal & Willis, George, 2022. "Using the web to predict regional trade flows: data extraction, modelling, and validation," OSF Preprints 9bu5z, Center for Open Science.
    17. Štefan Lyócsa & Petra Vašaničová & Branka Hadji Misheva & Marko Dávid Vateha, 2022. "Default or profit scoring credit systems? Evidence from European and US peer-to-peer lending markets," Financial Innovation, Springer;Southwestern University of Finance and Economics, vol. 8(1), pages 1-21, December.
    18. Arjan S. Gosal & Janine A. McMahon & Katharine M. Bowgen & Catherine H. Hoppe & Guy Ziv, 2021. "Identifying and Mapping Groups of Protected Area Visitors by Environmental Awareness," Land, MDPI, vol. 10(6), pages 1-14, May.
    19. Marcos Rodrigues & Fermín Alcasena & Pere Gelabert & Cristina Vega‐García, 2020. "Geospatial Modeling of Containment Probability for Escaped Wildfires in a Mediterranean Region," Risk Analysis, John Wiley & Sons, vol. 40(9), pages 1762-1779, September.
    20. Giovanny Pillajo-Quijia & Blanca Arenas-Ramírez & Camino González-Fernández & Francisco Aparicio-Izquierdo, 2020. "Influential Factors on Injury Severity for Drivers of Light Trucks and Vans with Machine Learning Methods," Sustainability, MDPI, vol. 12(4), pages 1-28, February.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51847-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.