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Cardiac mitochondrial function depends on BUD23 mediated ribosome programming.

Published version
Peer-reviewed

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Type

Article

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Authors

Poolman, Toryn 
Galli, Gina 
Pinali, Christian 

Abstract

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.

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Keywords

cardiac, cell biology, human, mitochondria, mouse, protein translation, ribosome, 5' Untranslated Regions, A549 Cells, Animals, Base Composition, Cardiomyopathies, Embryo, Mammalian, Female, Humans, Male, Methyltransferases, Mice, Mitochondria, Mitochondrial Proteins, Myocytes, Cardiac, Protein Interaction Maps, Ribosomes

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Medical Research Council (MC_UU_00015/4)
Medical Research Council (MC_UU_00015/7)