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.

中文翻译：

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心脏线粒体功能取决于BUD23介导的核糖体编程

在诸如心脏的具有高能量需求的组织中，需要有效的线粒体功能，而线粒体功能障碍与心血管疾病有关。响应内部和外部刺激，线粒体蛋白的表达受到严格调节。在这里，我们确定了一种新的机制，通过BUD23依赖性核糖体生成来调节线粒体的含量和功能。核糖体成熟，正常的18S / 28S化学计量和调节人A549细胞中线粒体转录本的翻译需要BUD23。删除Bud23鼠心肌细胞中的线粒体含量和功能降低，导致严重的心肌病和死亡。我们发现BUD23选择性地促进具有低GC含量的5'UTR的核糖体相互作用。两者合计，我们通过促进低5'UTR GC含量的mRNA转录物的有效翻译，确定BUD23在生物能学基因表达中的关键作用。BUD23成为小鼠发育和出生后心脏功能必不可少的。