CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs
| Autor: | Teresa Corona, Vangelis Kondylis, David Pla-Martín, Alberto Pessia, Ivan Nemazanyy, Peter Zentis, Astrid Schauss, Vidya Velagapudi, Elena I. Rugarli, Esther Barth, Henriette Hansen, Marie-Charlotte Marx, Désirée Schatton, Arnaud Mourier |
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| Přispěvatelé: | Institute for Molecular Medicine Finland |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oxidative phosphorylation Biology Mitochondrion METABOLOMICS Article Mitochondrial Proteins 03 medical and health sciences Mice 0302 clinical medicine Adenosine Triphosphate Cytosol Glucose homeostasis Animals Homeostasis Respiratory function RNA Messenger Research Articles RNA-Binding Proteins Translation (biology) Cell Biology Cell biology Mitochondria Mice Inbred C57BL Metabolic pathway 030104 developmental biology Metabolism Mitochondrial biogenesis Biochemistry Gene Expression Regulation CLUH Protein Biosynthesis 1182 Biochemistry cell and molecular biology RNA Interference Energy Metabolism 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | CLUH binds mRNAs implicated in intermediate metabolism and oxidative phosphorylation, but the physiological and molecular significance of these interactions is unclear. Schatton et al. use new constitutive and liver-specific Cluh knockouts to define the function of CLUH in catabolic and energy-converting pathways as a regulator of the translation and stability of target mRNAs. 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 mitochondria homologue (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 messenger RNAs. In the 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 fetal–neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions. |
| Databáze: | OpenAIRE |
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