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Cardiac mitochondrial function depends on BUD23 mediated ribosome programming
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002040/ https://www.ncbi.nlm.nih.gov/pubmed/31939735 http://dx.doi.org/10.7554/eLife.50705 |
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author | Baxter, Matthew Voronkov, Maria Poolman, Toryn Galli, Gina Pinali, Christian Goosey, Laurence Knight, Abigail Krakowiak, Karolina Maidstone, Robert Iqbal, Mudassar Zi, Min Prehar, Sukhpal Cartwright, Elizabeth J Gibbs, Julie Matthews, Laura C Adamson, Antony D Humphreys, Neil E Rebelo-Guiomar, Pedro Minczuk, Michal Bechtold, David A Loudon, Andrew Ray, David |
author_facet | Baxter, Matthew Voronkov, Maria Poolman, Toryn Galli, Gina Pinali, Christian Goosey, Laurence Knight, Abigail Krakowiak, Karolina Maidstone, Robert Iqbal, Mudassar Zi, Min Prehar, Sukhpal Cartwright, Elizabeth J Gibbs, Julie Matthews, Laura C Adamson, Antony D Humphreys, Neil E Rebelo-Guiomar, Pedro Minczuk, Michal Bechtold, David A Loudon, Andrew Ray, David |
author_sort | Baxter, Matthew |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7002040 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70020402020-02-06 Cardiac mitochondrial function depends on BUD23 mediated ribosome programming Baxter, Matthew Voronkov, Maria Poolman, Toryn Galli, Gina Pinali, Christian Goosey, Laurence Knight, Abigail Krakowiak, Karolina Maidstone, Robert Iqbal, Mudassar Zi, Min Prehar, Sukhpal Cartwright, Elizabeth J Gibbs, Julie Matthews, Laura C Adamson, Antony D Humphreys, Neil E Rebelo-Guiomar, Pedro Minczuk, Michal Bechtold, David A Loudon, Andrew Ray, David eLife Cell Biology 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. eLife Sciences Publications, Ltd 2020-01-15 /pmc/articles/PMC7002040/ /pubmed/31939735 http://dx.doi.org/10.7554/eLife.50705 Text en © 2020, Baxter et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Baxter, Matthew Voronkov, Maria Poolman, Toryn Galli, Gina Pinali, Christian Goosey, Laurence Knight, Abigail Krakowiak, Karolina Maidstone, Robert Iqbal, Mudassar Zi, Min Prehar, Sukhpal Cartwright, Elizabeth J Gibbs, Julie Matthews, Laura C Adamson, Antony D Humphreys, Neil E Rebelo-Guiomar, Pedro Minczuk, Michal Bechtold, David A Loudon, Andrew Ray, David Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title_full | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title_fullStr | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title_full_unstemmed | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title_short | Cardiac mitochondrial function depends on BUD23 mediated ribosome programming |
title_sort | cardiac mitochondrial function depends on bud23 mediated ribosome programming |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002040/ https://www.ncbi.nlm.nih.gov/pubmed/31939735 http://dx.doi.org/10.7554/eLife.50705 |
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