title: Identification of potential mitochondrial CLPXP protease interactors and substrates suggests its central role in energy metabolism.
abstract: Maintenance of mitochondria is achieved by several mechanisms, including the regulation of mitochondrial proteostasis. The matrix protease CLPXP, involved in protein quality control, has been implicated in ageing and disease. However, particularly due to the lack of knowledge of CLPXP's substrate spectrum, only little is known about the pathways and mechanisms controlled by this protease. Here we report the first comprehensive identification of potential mitochondrial CLPXP in vivo interaction partners and substrates using a combination of tandem affinity purification and differential proteomics. This analysis reveals that CLPXP in the fungal ageing model Podospora anserina is mainly associated with metabolic pathways in mitochondria, e.g. components of the pyruvate dehydrogenase complex and the tricarboxylic acid cycle as well as subunits of electron transport chain complex I. These data suggest a possible function of mitochondrial CLPXP in the control and/or maintenance of energy metabolism. Since bioenergetic alterations are a common feature of neurodegenerative diseases, cancer, and ageing, our data comprise an important resource for specific studies addressing the role of CLPXP in these adverse processes.
authors.affiliation: Johann Wolfgang Goethe University, Faculty for Biosciences &Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute for Molecular Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Fischer
authors.affiliation: Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt, Germany.
authors.forename: Julian D
authors.initials: JD
authors.lastname: Langer
authors.affiliation: Johann Wolfgang Goethe University, Faculty for Biosciences &Cluster of Excellence 'Macromolecular Complexes' Frankfurt, Institute for Molecular Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
mesh_terms: D002952:Citric Acid Cycle; D042967:Electron Transport Complex I / Q000378:metabolism; D049071:Endopeptidase Clp / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008928:Mitochondria / Q000201:enzymology*; D016296:Mutagenesis; D048468:Podospora / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013379:Substrate Specificity
chemical_list: D005656:Fungal Proteins; D011994:Recombinant Proteins; C568646:ClpP protein, human; D049071:Endopeptidase Clp; D042967:Electron Transport Complex I