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Role of CLPXP protease in energy metabolism

December 2015. Mitochondria are essential eukaryotic organelles involved in different metabolic processes like energy conversion or the synthesis of iron sulfur clusters, in cellular signalling and the control of cell death. Owing to their central role in cellular physiology, dysfunction of mitochondria and changes in mitochondrial bioenergetics are a common feature of neurodegenerative diseases, cancer and ageing. A complex network of different quality control pathways is active in an effort to maintain mitochondrial function and adapt it to stress conditions. In this network, mitochondrial proteases are increasingly recognized as important regulatory components.

The matrix protease CLPXP, involved in protein quality control, has been implicated in ageing and disease. In the fungal ageing model Podospora anserina, deletion of the gene PaClpP, encoding the proteolytic subunit of CLPXP, led to an unexpected increase of the mutant strain’s healthy lifespan. It was possible to revert this longevity phenotype by expression of human ClpP in the fungal deletion background, demonstrating functional conservation of human and fungal CLPP. However, particularly due to the lack of knowledge of CLPXP’s substrate spectrum, little is known about the pathways and mechanisms controlled by this protease. A team of Frankfurt scientists lead by Heinz Osiewaz now reports the first comprehensive identification of potential mitochondrial CLPXP in vivo interaction partners and substrates. Their analysis reveals that P. anserina CLPXP 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. More ...


Heinz Osiewacz
Institute of Molecular Biosciences
Goethe University Frankfurt


Full references:
Fischer F, Langer JD, Osiewacz HD (2015) Identification of potential mitochondrial CLPXP protease interactors and substrates suggests its central role in energy metabolism. Sci Rep 5, article no. 18375, doi: 10.1038/srep18375. Link ...