Identification of potential mitochondrial CLPXP protease interactors and substrates suggests its central role in energy metabolism

• Published in: Scientific reports Vol. 5; no. 1; p. 18375
• Main Authors: Fischer, Fabian, Langer, Julian D., Osiewacz, Heinz D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.12.2015; Nature Publishing Group
• Subjects: 631/337/475; 631/45/468; 631/80/642/333; 82; 82/58; 82/83; Aging; Cancer; Citric Acid Cycle; Electron transport; Electron transport chain; Electron Transport Complex I - metabolism; Endopeptidase Clp - chemistry; Endopeptidase Clp - genetics; Endopeptidase Clp - metabolism; Energy metabolism; Energy Metabolism - physiology; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Humanities and Social Sciences; Humans; Mass Spectrometry; Metabolic pathways; Metabolism; Mitochondria; Mitochondria - enzymology; multidisciplinary; Mutagenesis; Neurodegenerative diseases; Podospora - metabolism; Proteinase; Proteomics; Pyruvate dehydrogenase (lipoamide); Pyruvic acid; Quality control; Recombinant Proteins - biosynthesis; Recombinant Proteins - isolation & purification; Science; Substrate Specificity; Tricarboxylic acid cycle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18375

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.