Cardiac mitochondrial function depends on BUD23 mediated ribosome programming
| Title: | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
|---|---|
| Authors: | Matthew Baxter, Maria Voronkov, Toryn Poolman, Gina Galli, Christian Pinali, Laurence Goosey, Abigail Knight, Karolina Krakowiak, Robert Maidstone, Mudassar Iqbal, Min Zi, Sukhpal Prehar, Elizabeth J Cartwright, Julie Gibbs, Laura C Matthews, Antony D Adamson, Neil E Humphreys, Pedro Rebelo-Guiomar, Michal Minczuk, David A Bechtold, Andrew Loudon, David Ray |
| Source: | eLife, Vol 9 (2020) |
| Publisher Information: | eLife Sciences Publications Ltd, 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | mitochondria, protein translation, cardiac, ribosome, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation. BUD23 was required for ribosome maturation, normal 18S/28S stoichiometry and modulated the translation of mitochondrial transcripts in human A549 cells. Deletion of Bud23 in murine cardiomyocytes reduced mitochondrial content and function, leading to severe cardiomyopathy and death. We discovered that BUD23 selectively promotes ribosomal interaction with low GC-content 5’UTRs. Taken together we identify a critical role for BUD23 in bioenergetics gene expression, by promoting efficient translation of mRNA transcripts with low 5’UTR GC content. BUD23 emerges as essential to mouse development, and to postnatal cardiac function. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/50705; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.50705 |
| Access URL: | https://doaj.org/article/c80495bec8114315bceead7ae22ca77e |
| Accession Number: | edsdoj.80495bec8114315bceead7ae22ca77e |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.50705 |
| Published in: | eLife |
| Language: | English |