title: The novel mitochondrial matrix protease Ste23 is required for efficient presequence degradation and processing.
abstract: Approximately 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which are cleaved upon exposure to the mitochondrial processing protease MPP in the matrix. Cleaved presequence peptides then need to be efficiently degraded, and impairment of this clearance step, for example, by amyloid β peptides, causes feedback inhibition of MPP, leading ultimately to accumulation of immature precursor proteins within mitochondria. Degradation of mitochondrial peptides is performed by Cym1 in yeast and its homologue, PreP, in humans. Here we identify the novel mitochondrial matrix protease Ste23 in yeast, a homologue of human insulin-degrading enzyme, which is required for efficient peptide degradation. Ste23 and Cym1 tightly cooperate to ensure the correct functioning of the essential presequence processing machinery.
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.|Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Asli Aras
authors.initials: AA
authors.lastname: Taskin
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Cansu
authors.initials: C
authors.lastname: Kücükköse
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Burger
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mossmann
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany chris.meisinger@biochemie.uni-freiburg.de.|Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany.|Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: F-Nora
authors.initials: FN
authors.lastname: Vögtle
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D062106:Protein Degradation End Products / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D000096122:Mitochondrial Processing Peptidase
chemical_list: D008666:Metalloendopeptidases; D045726:Metalloproteases; D010455:Peptides; D062106:Protein Degradation End Products; D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; D000096122:Mitochondrial Processing Peptidase; C501750:CYM1 protein, S cerevisiae; C503912:Ste23 protein, S cerevisiae