Cell lineage-specific mitochondrial resilience during mammalian organogenesis
| Autor: | Stephen P. Burr, Florian Klimm, Angelos Glynos, Malwina Prater, Pamella Sendon, Pavel Nash, Christopher A. Powell, Marie-Lune Simard, Nina A. Bonekamp, Julia Charl, Hector Diaz, Lyuba V. Bozhilova, Yu Nie, Haixin Zhang, Michele Frison, Maria Falkenberg, Nick Jones, Michal Minczuk, James B. Stewart, Patrick F. Chinnery |
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| Přispěvatelé: | Chinnery, Patrick [0000-0002-7065-6617], Apollo - University of Cambridge Repository |
| Rok vydání: | 2023 |
| Předmět: |
Mitochondrial Diseases
mtDNA Organogenesis Embryonic Development mt-Ta 500 Naturwissenschaften und Mathematik::570 Biowissenschaften Biologie::570 Biowissenschaften Biologie single-cell Embryo Mammalian OXPHOS DNA Mitochondrial General Biochemistry Genetics and Molecular Biology Mitochondria Mice Pregnancy Organ Specificity SCENIC Animals Humans Female Cell Lineage RNA-seq |
| Zdroj: | Cell 1229.E21 |
| DOI: | 10.17863/cam.93286 |
| Popis: | 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 mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription 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. |
| Databáze: | OpenAIRE |
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