Proteomics

Dataset Information

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CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs


ABSTRACT: Mitochondria are essential organelles that host crucial metabolic pathways and produce ATP. The mitochondrial proteome is heterogeneous among tissues, and can dynamically change in response to different metabolic conditions. While the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well-known, post-transcriptional regulatory mechanisms remain unclear. Here we show that the cytosolic RNA-binding protein CLUH regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target mRNAs. In absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the foetal-neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light into post-transcriptional mechanisms controlling the expression of mitochondrial proteins, and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Christian Frese  

LAB HEAD: Christian K. Frese

PROVIDER: PXD005628 | Pride | 2017-02-08

REPOSITORIES: Pride

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Publications


Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondri  ...[more]

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