title: CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs.
abstract: 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 ofCluh, 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.
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Schatton
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: David
authors.identifier: 0000-0002-5189-0723
authors.initials: D
authors.lastname: Pla-Martin
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Marx
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Hansen
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Arnaud
authors.identifier: 0000-0002-5413-611X
authors.initials: A
authors.lastname: Mourier
authors.affiliation: Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Nemazanyy
authors.affiliation: Metabolomics Unit, Institute for Molecular Medicine Finland, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Alberto
authors.identifier: 0000-0001-8607-9191
authors.initials: A
authors.lastname: Pessia
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Zentis
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Corona
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Vangelis
authors.identifier: 0000-0002-6970-8731
authors.initials: V
authors.lastname: Kondylis
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Esther
authors.identifier: 0000-0002-4678-2365
authors.initials: E
authors.lastname: Barth
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Schauss
authors.affiliation: Metabolomics Unit, Institute for Molecular Medicine Finland, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Vidya
authors.initials: V
authors.lastname: Velagapudi
authors.affiliation: Institute for Genetics, University of Cologne, 50674 Cologne, Germany elena.rugarli@uni-koeln.de.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
authors.forename: Elena I
authors.identifier: 0000-0002-5782-1067
authors.initials: EI
authors.lastname: Rugarli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000378:metabolism / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D008660:Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000255:Adenosine Triphosphate