PMID:19837041

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
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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

References

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