title: Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability.
abstract: Many mitochondrial proteins are synthesized with N-terminal presequences that are removed by specific peptidases. The N-termini of the mature proteins and thus peptidase cleavage sites have only been determined for a small fraction of mitochondrial proteins and yielded a controversial situation for the cleavage site specificity of the major mitochondrial processing peptidase (MPP). We report a global analysis of the N-proteome of yeast mitochondria, revealing the N-termini of 615 different proteins. Significantly more proteins than predicted contained cleavable presequences. We identified the intermediate cleaving peptidase Icp55, which removes an amino acid from a characteristic set of MPP-generated N-termini, solving the controversial situation of MPP specificity and suggesting that Icp55 converts instable intermediates into stable proteins. Our results suggest that Icp55 is critical for stabilization of the mitochondrial proteome and illustrate how the N-proteome can serve as rich source for a systematic analysis of mitochondrial protein targeting, cleavage and turnover.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: F-Nora
authors.initials: FN
authors.lastname: Vögtle
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wortelkamp
authors.forename: René P
authors.initials: RP
authors.lastname: Zahedi
authors.forename: Dorothea
authors.initials: D
authors.lastname: Becker
authors.forename: Claudia
authors.initials: C
authors.lastname: Leidhold
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.forename: Josef
authors.initials: J
authors.lastname: Kellermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
mesh_terms: D006801:Humans; D008928:Mitochondria / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000032:analysis*; D010447:Peptide Hydrolases / Q000378:metabolism; D055550:Protein Stability; D020543:Proteome / Q000032:analysis*; D012441:Saccharomyces cerevisiae / Q000737:chemistry*
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome; D010447:Peptide Hydrolases