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Baxter 2020 Elife

From Bioblast
Publications in the MiPMap
Baxter M, Voronkov M, Poolman T, Galli G, Pinali C, Goosey L, Knight A, Krakowiak K, Maidstone R, Iqbal M, Zi M, Prehar S, Cartwright EJ, Gibbs J, Matthews LC, Adamson AD, Humphreys NE, Rebelo-Guiomar P, Minczuk M, Bechtold DA, Loudon A, Ray D (2020) Cardiac mitochondrial function depends on BUD23 mediated ribosome programming. Elife 9:e50705.

Β» PMID: 31939735 Open Access

Baxter M, Voronkov M, Poolman T, Galli G, Pinali C, Goosey L, Knight A, Krakowiak K, Maidstone R, Iqbal M, Zi M, Prehar S, Cartwright EJ, Gibbs J, Matthews LC, Adamson AD, Humphreys NE, Rebelo-Guiomar P, Minczuk M, Bechtold DA, Loudon A, Ray D (2020) Elife

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.

Β© 2019, Baxter et al. β€’ Keywords: Cell biology, Human, Mouse β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: UK Manchester Galli GL


Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Heart  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

Labels, 2020-01, AmR