mRNA trafficking directs cell-size-scaling of mitochondria distribution and function
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 di...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61940-6 |
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| _version_ | 1849764113134125056 |
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| author | Joshua J. Bradbury Georgia E. Hulmes Ranjith Viswanathan Guilherme Costa Holly E. Lovegrove Shane P. Herbert |
| author_facet | Joshua J. Bradbury Georgia E. Hulmes Ranjith Viswanathan Guilherme Costa Holly E. Lovegrove Shane P. Herbert |
| author_sort | Joshua J. Bradbury |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-44ed5e89caa84f65ac8f0b59a4189dee |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-44ed5e89caa84f65ac8f0b59a4189dee2025-08-20T03:05:14ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61940-6mRNA trafficking directs cell-size-scaling of mitochondria distribution and functionJoshua J. Bradbury0Georgia E. Hulmes1Ranjith Viswanathan2Guilherme Costa3Holly E. Lovegrove4Shane P. Herbert5Faculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadFaculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadFaculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadFaculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadFaculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadFaculty of Biology, Medicine and Health, Michael Smith Building, University of Manchester, Oxford RoadAbstract 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.https://doi.org/10.1038/s41467-025-61940-6 |
| spellingShingle | Joshua J. Bradbury Georgia E. Hulmes Ranjith Viswanathan Guilherme Costa Holly E. Lovegrove Shane P. Herbert mRNA trafficking directs cell-size-scaling of mitochondria distribution and function Nature Communications |
| title | mRNA trafficking directs cell-size-scaling of mitochondria distribution and function |
| title_full | mRNA trafficking directs cell-size-scaling of mitochondria distribution and function |
| title_fullStr | mRNA trafficking directs cell-size-scaling of mitochondria distribution and function |
| title_full_unstemmed | mRNA trafficking directs cell-size-scaling of mitochondria distribution and function |
| title_short | mRNA trafficking directs cell-size-scaling of mitochondria distribution and function |
| title_sort | mrna trafficking directs cell size scaling of mitochondria distribution and function |
| url | https://doi.org/10.1038/s41467-025-61940-6 |
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