Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability.
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.
Vögtle
F-Nora
FN
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Wortelkamp
Stefanie
S
Zahedi
René P
RP
Becker
Dorothea
D
Leidhold
Claudia
C
Gevaert
Kris
K
Kellermann
Josef
J
Voos
Wolfgang
W
Sickmann
Albert
A
Pfanner
Nikolaus
N
Meisinger
Chris
C
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*
D024101:Mitochondrial Proteins; D020543:Proteome; D010447:Peptide Hydrolases