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The Mouse Heart Mitochondria N Terminome Provides Insights into ClpXP-Mediated Proteolysis
Authors:Eduard Hofsetz  Fatih Demir  Karolina Szczepanowska  Alexandra Kukat  Jayachandran N Kizhakkedathu  Aleksandra Trifunovic  Pitter F Huesgen
Institution:1. Institute for Mitochondrial Diseases and Aging at CECAD Research Centre, and Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany;2. Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Cologne, Germany, Medical Faculty and University Hospital, University of Cologne, Cologne, Germany;3. Central Institute for Engineering, Electronics and Analytics, ZEA-3, Forschungszentrum Jülich, Germany;4. Centre for Blood Research, School of Biomedical Engineering, Department of Pathology & Laboratory Medicine, Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada;5. Institute for Biochemistry, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany
Abstract:
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  • Highlights
    • •Mitochondrial heart N terminome shows aminopeptidase processing after MTS cleavage.
    • •CLPP-deficiency alters protein processing patterns in mouse heart mitochondria.
    • •Candidate substrates identified by N termini accumulation and interaction with inactive ClpXP.
    • •UQCRC1, HSPA9 and OAT validated biochemically as high confidence ClpXP substrates.
    Keywords:Proteolysis  degradomics  mitochondria function or biology  affinity proteomics  substrate identification
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