A cryptic matrix targeting signal of the yeast ADP/ATP carrier normally inserted by the TIM22 complex is recognized by the TIM23 machinery.
The yeast ADP/ATP carrier (AAC) is a mitochondrial protein that is targeted to the inner membrane via the TIM10 and TIM22 translocase complexes. AAC is devoid of a typical mitochondrial targeting signal and its targeting and insertion are thought to be guided by internal amino acid sequences. Here we show that AAC contains a cryptic matrix targeting signal that can target up to two thirds of the N-terminal part of the protein to the matrix. This event is coordinated by the TIM23 translocase and displays all the features of the matrix-targeting pathway. However, in the context of the whole protein, this signal is 'masked' and rendered non-functional as the polypeptide is targeted to the inner membrane via the TIM10 and TIM22 translocases. Our data suggest that after crossing the outer membrane the whole polypeptide chain of AAC is necessary to commit the precursor to the TIM22-mediated inner membrane insertion pathway.
School of Biological Sciences, Michael Smith Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Maïlys A S
MA
Vergnolle
Helen
H
Sawney
Tina
T
Junne
Luisita
L
Dolfini
Kostas
K
Tokatlidis
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D018834:Chaperonin 60; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; C100674:TIM12 protein, S cerevisiae; C102549:TIM22 protein, S cerevisiae; C083081:TIM23 protein, S cerevisiae; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases