title: CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.
abstract: Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)-binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Schatton
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Paola
authors.initials: P
authors.lastname: Martinelli
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Hansen
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Pla-Martin
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Barth
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmueller
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030.
authors.forename: Marco
authors.initials: M
authors.lastname: Sardiello
authors.affiliation: Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany Institute for Genetics, Center for Molecular Medicine, Cologne Center for Genomics, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50923 Cologne, Germany Elena.Rugarli@uni-koeln.de.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Rugarli
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014404:Tubulin / Q000032:analysis / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014404:Tubulin