Abstract
Cluh is a cytosolic protein that is known to specifically bind the mRNAs of nuclear-encoded mitochondrial proteins and play critical roles in mitochondrial biogenesis. Here, we report the role of Cluh in adipogenesis. Our study shows that mRNA expression of Cluh is stimulated during adipogenesis, and that cAMP/Creb signalling increases its transcription. Cluh depletion impaired proper adipocyte differentiation, with reductions seen in lipid droplets and adipogenic marker gene expression. Interestingly, the inductions of the brown adipocyte-specific genes, Ucp1, Cidea and Cox7a1, are severely blocked by Cluh depletion during brown adipogenesis. Mitochondrial respiration and the stability of mRNAs encoding mitochondrial proteins are reduced by Cluh depletion during brown adipogenesis. These results suggest that Cluh, which is induced during adipogenesis, promotes the post-transcriptional regulation of mitochondrial proteins and supports differentiation.
Highlights
Mitochondrial biogenesis is up-regulated during adipocyte differentiation and promotes this process[1,2]
Since CLUH has been known to be a post-transcriptional regulator of mitochondrial protein, we hypothesized that it may play a crucial role in adipocytes, where the activity of mitochondria is increased[1,2,3,4]
We examined whether the function of Cluh during adipogenesis and in adipocytes was related to its known ability to regulate mitochondrial biogenesis[7,13]
Summary
Mitochondrial biogenesis is up-regulated during adipocyte differentiation and promotes this process[1,2]. The mitochondrial density increases and structural and biochemical alterations are seen in both brown and white adipose cells[3]. Wilson-Fritch et al had reported 20–30-fold increase in concentration of numerous mitochondrial proteins during the differentiation of 3T3-L1 cells[4]. Depletion of Cluh decreased lipid droplets and reduced the transcription of adipocyte marker proteins. The expression of brown adipocyte marker genes was severely impaired by depletion of CLUH from C3H10T1/2 cells; such cells exhibit mitochondrial dysfunction during adipogenesis, related to the impaired expression of mitochondrial mRNAs. The reduction of transcripts in CLUH-depleted adipocytes was associated with a decrease in mRNA stability
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