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PMID:19837041

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Citation

Vögtle, FN, Wortelkamp, S, Zahedi, RP, Becker, D, Leidhold, C, Gevaert, K, Kellermann, J, Voos, W, Sickmann, A, Pfanner, N and Meisinger, C (2009) Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139:428-39

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.

Links

PubMed Online version:10.1016/j.cell.2009.07.045

Keywords

Humans; Mitochondria/chemistry; Mitochondrial Proteins/analysis; Peptide Hydrolases/metabolism; Protein Stability; Proteome/analysis; Saccharomyces cerevisiae/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:ICP55

located_in

GO:0031314: extrinsic component of mitochondrial inner membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:ICP55

involved_in

GO:0016485: protein processing

ECO:0000316: genetic interaction evidence used in manual assertion

SGD:S000001617
SGD:S000004153

P

Seeded From UniProt

complete

YEAST:ICP55

involved_in

GO:0050821: protein stabilization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:ICP55

enables

GO:0004177: aminopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:ICP55

involved_in

GO:0016485: protein processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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