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mRNA trafficking directs cell-size-scaling of mitochondria distribution and function

Author

Listed:
  • Joshua J. Bradbury

    (University of Manchester, Oxford Road
    King’s College London)

  • Georgia E. Hulmes

    (University of Manchester, Oxford Road)

  • Ranjith Viswanathan

    (University of Manchester, Oxford Road)

  • Guilherme Costa

    (University of Manchester, Oxford Road
    Queen’s University Belfast)

  • Holly E. Lovegrove

    (University of Manchester, Oxford Road)

  • Shane P. Herbert

    (University of Manchester, Oxford Road)

Abstract

The subcellular positioning of organelles is critical to their function and is dynamically adapted to changes in cell morphology. Yet, how cells sense shifts in their dimensions and redistribute organelles accordingly remains unclear. Here we reveal that cell-size-scaling of mitochondria distribution and function is directed by polarised trafficking of mRNAs. We identify a 29 bp 3’UTR motif in mRNA encoding TRAK2, a key determinant of mitochondria retrograde transport, that promotes cell-size-dependent targeting of TRAK2 mRNA to distal sites of cell protrusions. Cell-size-scaled mRNA polarisation in turn scales mitochondria distribution by defining the precise site of TRAK2-MIRO1 retrograde transport complex assembly. Consequently, 3’UTR motif excision perturbs size-regulated transport and eradicates scaling of mitochondria positioning, triggering distal accumulation of mitochondria and progressive hypermotility as cells increase size. Together, our results reveal an RNA-driven mechanistic basis for the cell-size-scaling of organelle distribution and function that is critical to homeostatic control of motile cell behaviour.

Suggested Citation

  • Joshua J. Bradbury & Georgia E. Hulmes & Ranjith Viswanathan & Guilherme Costa & Holly E. Lovegrove & Shane P. Herbert, 2025. "mRNA trafficking directs cell-size-scaling of mitochondria distribution and function," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61940-6
    DOI: 10.1038/s41467-025-61940-6
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    References listed on IDEAS

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    1. Verena Henrichs & Lenka Grycova & Cyril Barinka & Zuzana Nahacka & Jiri Neuzil & Stefan Diez & Jakub Rohlena & Marcus Braun & Zdenek Lansky, 2020. "Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Stavroula Mili & Konstadinos Moissoglu & Ian G. Macara, 2008. "Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions," Nature, Nature, vol. 453(7191), pages 115-119, May.
    3. Alex D Herbert & Antony M Carr & Eva Hoffmann, 2014. "FindFoci: A Focus Detection Algorithm with Automated Parameter Training That Closely Matches Human Assignments, Reduces Human Inconsistencies and Increases Speed of Analysis," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-33, December.
    4. Adam R. Fenton & Thomas A. Jongens & Erika L. F. Holzbaur, 2021. "Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Andrew S. Moore & Stephen M. Coscia & Cory L. Simpson & Fabian E. Ortega & Eric C. Wait & John M. Heddleston & Jeffrey J. Nirschl & Christopher J. Obara & Pedro Guedes-Dias & C. Alexander Boecker & Te, 2021. "Actin cables and comet tails organize mitochondrial networks in mitosis," Nature, Nature, vol. 591(7851), pages 659-664, March.
    6. Nida Siddiqui & Alexander James Zwetsloot & Alice Bachmann & Daniel Roth & Hamdi Hussain & Jonathan Brandt & Irina Kaverina & Anne Straube, 2019. "PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    7. John T. Canty & Andrew Hensley & Merve Aslan & Amanda Jack & Ahmet Yildiz, 2023. "TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
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