Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


The power of translation

Credit: J.Vallis/NPG

Cellular energy is mostly derived from mitochondrion-generated ATP. The brain requires high amounts of energy, underlining the importance of proper regulation of mitochondrial activity for normal brain function. Richter and colleagues now show that a key regulator of such activity is cytoplasmic polyadenylation element binding protein 1 (CPEB1), which is known to promote protein translation.

CPEB1 binds to well-defined sequences — the so-called cytoplasmic polyadenylation elements (CPEs) — in the 3′ untranslated regions (UTRs) of specific mRNAs, inducing mRNA polyadenylation and translation. Previous studies showed that fibroblasts depleted in CPEB1 exhibited a reduction in mitochondrial ATP production, suggesting that CPEB1 regulates mitochondrial protein function.

The authors first examined whether the absence of CPEB1 in tissues causes bioenergtic defects. Brain tissue, but not liver or muscle tissue, from Cpeb1−/− mice showed a marked reduction in ATP levels. A decrease in ATP levels could also be induced in wild-type neurons by knocking down CPEB1 expression with short hairpin RNAs (shRNAs). Thus, these data suggest that CPEB1 is an important regulator of ATP production in neurons.

Brain tissue, but not liver or muscle tissue, from Cpeb1−/− mice showed a marked reduction in ATP levels

Further experiments revealed that oxygen consumption — necessary for mitochondrial electron transport — was decreased in Cpeb1−/− brain tissue and cultured primary neurons. However, lactate generation, which is a marker of glycolysis, and mitochondrial number were unaffected in Cpeb1−/− neurons, indicating that CPEB1 removal specifically impairs mitochondrial ATP generation.

The authors isolated mitochondria from wild-type and knockout mouse brains and assessed the activities of the four mitochondrial protein complexes that are involved in the electron transport chain in in vitro assays. Cpeb1−/− mitochondria had markedly lower complex I activity than did wild-type mitochondria, and this reduction was associated with a decrease in total brain levels of NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2), which is a key component of complex I. As lentivirus-mediated expression of NDUFV2 in Cpeb1−/− neurons restored ATP levels to wild-type levels, these data indicate that knocking out Cpeb1 impairs mitochondrial function in neurons by causing low NDUFV2 expression.

Ndufv2 mRNA levels in Cpeb1−/− mouse brain tissue were present at wild-type levels, suggesting that CPEB1 regulates NDUFV2 expression, at least in part, by a post-transcriptional mechanism, in line with the known activity of CPEB1. Indeed, Ndufv2 mRNA contains several 3′ UTR CPEs, and the authors showed that these are important for NDUFV2 expression in a reporter assay. Of note, Ndufv2 transcripts from Cpeb1−/− mouse brain tissue had shorter poly(A) tails than those from wild-type brain tissue, further indicating that CPEB1 post-transcriptionally regulates NDUFV2 expression.

The authors examined the effects of knocking out Cpeb1 on neuronal development in cultured primary neurons. After 5 days in culture, Cpeb1−/− neurons exhibited fewer dendritic branches and shorter dendrites than did wild-type neurons. These defects seemed to be directly caused by reduced ATP production, as phosphocreatine treatment, which increases ATP levels, rescued the dendritic branching phenotype in Cpeb1−/− neurons. The dendritic defects could be reproduced in vivo by knocking down the levels of CPEB1 in the dentate gyrus of young wild-type mice through retrovirus-mediated expression of Cpeb1 shRNAs. Interestingly, these defects could be rescued by ectopic expression of NDUFV2.

Taken together, these results indicate that, in the brain, CPEB1 promotes mitochondrial ATP production by increasing Ndufv2 mRNA translation and that this pathway is crucial for normal neuronal development.


  1. Oruganty-Das, A. et al. Translational control of mitochondrial energy production mediates neuron morphogenesis. Cell Metab. 16, 789–800 (2012)

    CAS  Article  Google Scholar 

Download references


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yates, D. The power of translation. Nat Rev Neurosci 14, 81 (2013).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing