title: CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels.
abstract: Despite being one of the most studied proteases in bacteria, very little is known about the role of ClpXP in mitochondria. We now present evidence that mammalian CLPP has an essential role in determining the rate of mitochondrial protein synthesis by regulating the level of mitoribosome assembly. Through a proteomic approach and the use of a catalytically inactive CLPP, we produced the first comprehensive list of possible mammalian ClpXP substrates involved in the regulation of mitochondrial translation, oxidative phosphorylation, and a number of metabolic pathways. We further show that the defect in mitoribosomal assembly is a consequence of the accumulation of ERAL1, a putative 12S rRNA chaperone, and novel ClpXP substrate. The presented data suggest that the timely removal of ERAL1 from the small ribosomal subunit is essential for the efficient maturation of the mitoribosome and a normal rate of mitochondrial translation.
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Karolina
authors: K
authors: Szczepanowska
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Priyanka
authors: 0000-0003-4207-0341
authors: P
authors: Maiti
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Alexandra
authors: A
authors: Kukat
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Eduard
authors: E
authors: Hofsetz
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Genetics, University of Cologne, Cologne, Germany.
authors: Hendrik
authors: H
authors: Nolte
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Katharina
authors: K
authors: Senft
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Christina
authors: C
authors: Becker
authors: Max Planck Institute for Biology of Aging, Cologne, Germany.
authors: Benedetta
authors: B
authors: Ruzzenente
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Vegetative Physiology, University of Cologne, Cologne, Germany.
authors: Hue-Tran
authors: HT
authors: Hornig-Do
authors: Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Rolf
authors: R
authors: Wibom
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Vegetative Physiology, University of Cologne, Cologne, Germany.
authors: Rudolf J
authors: RJ
authors: Wiesner
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.|Institute for Genetics, University of Cologne, Cologne, Germany.
authors: Marcus
authors: M
authors: Krüger
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany aleksandra.trifunovic@uk-koeln.de.|Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
authors: Aleksandra
authors: 0000-0002-5472-3517
authors: A
authors: Trifunovic
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049071:Endopeptidase Clp / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: C540137:Era protein, mouse; D016601:RNA-Binding Proteins; C000589752:CLPP protein, mouse; D049071:Endopeptidase Clp; D019204:GTP-Binding Proteins
keywords: 
  CLPP
  ; ERAL1; OXPHOS deficiency; mitochondrial ribosome assembly