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Cell lineage-specific mitochondrial resilience during mammalian organogenesis
- Burr, S. P. (author)
- Klimm, F. (author)
- Glynos, A. (author)
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- Prater, M. (author)
- Sendon, P. (author)
- Nash, P. (author)
- Powell, C. A. (author)
- Simard, M. L. (author)
- Bonekamp, N. A. (author)
- Charl, J. (author)
- Bozhilova, L. V. (author)
- Nie, Y. (author)
- Zhang, H. X. (author)
- Frison, M. (author)
- Jones, N. (author)
- Minczuk, M. (author)
- Stewart, J. B. (author)
- Chinnery, P. F. (author)
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- (creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
- In: Cell. - : Elsevier BV. - 0092-8674. ; 186:6
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mito-chondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic devel-opment. The compensatory pathways were both tissue and mutation specific and under the control of tran-scription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- comprehensive analysis
- transcription factors
- stress-response
- DNA
- mutations
- rna
- biogenesis
- disorders
- regulator
- identity
- package
- Biochemistry & Molecular Biology
- Cell Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
- Burr, S. P.
- Klimm, F.
- Glynos, A.
- Prater, M.
- Sendon, P.
- Nash, P.
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- Powell, C. A.
- Simard, M. L.
- Bonekamp, N. A.
- Charl, J.
- Diaz-Maldonado, ...
- Bozhilova, L. V.
- Nie, Y.
- Zhang, H. X.
- Frison, M.
- Falkenberg, Mari ...
- Jones, N.
- Minczuk, M.
- Stewart, J. B.
- Chinnery, P. F.
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- About the subject
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- NATURAL SCIENCES
- NATURAL SCIENCES
- and Biological Scien ...
- Articles in the publication
- Cell
- By the university
- University of Gothenburg
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