Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins.
Mitochondria consist of four compartments-outer membrane, intermembrane space, inner membrane, and matrix--with crucial but distinct functions for numerous cellular processes. A comprehensive characterization of the proteome of an individual mitochondrial compartment has not been reported so far. We used a eukaryotic model organism, the yeast Saccharomyces cerevisiae, to determine the proteome of highly purified mitochondrial outer membranes. We obtained a coverage of approximately 85% based on the known outer membrane proteins. The proteome represents a rich source for the analysis of new functions of the outer membrane, including the yeast homologue (Hfd1/Ymr110c) of the human protein causing Sjögren-Larsson syndrome. Surprisingly, a subclass of proteins known to reside in internal mitochondrial compartments were found in the outer membrane proteome. These seemingly mislocalized proteins included most top scorers of a recent genome-wide analysis for mRNAs that were targeted to mitochondria and coded for proteins of prokaryotic origin. Together with the enrichment of the precursor form of a matrix protein in the outer membrane, we conclude that the mitochondrial outer membrane not only contains resident proteins but also accumulates a conserved subclass of preproteins destined for internal mitochondrial compartments.
Zahedi
Rene P
RP
Rudolf-Virchow-Center for Experimental Biomedicine, Universität Würzburg, D-97078 Würzburg, Germany.
Sickmann
Albert
A
Boehm
Andreas M
AM
Winkler
Christiane
C
Zufall
Nicole
N
Schönfisch
Birgit
B
Guiard
Bernard
B
Pfanner
Nikolaus
N
Meisinger
Chris
C
D000445:Aldehyde Oxidoreductases / Q000737:chemistry; D000595:Amino Acid Sequence; D015180:Electrophoresis, Gel, Two-Dimensional; D016681:Genome, Fungal; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000032:analysis / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D022161:Transport Vesicles / Q000378:metabolism
D024101:Mitochondrial Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase