N-terminal hydrophobic sorting signals of preproteins confer mitochondrial hsp70 independence for import into mitochondria.
The requirement of mitochondrial hsp70 (mt-hsp70) for the import of a series of preproteins containing hydrophobic sorting signals into isolated yeast mitochondria was investigated. Here we demonstrate that the presence of such a sorting signal in proximity to the N-terminal matrix-targeting sequence of a preprotein can secure a translocating polypeptide chain in the import channel in a manner that does not require mt-hsp70 activity. Trapping the translocating chain in this fashion leads to efficient processing by the mitochondrial processing peptidase and to complete translocation across the outer mitochondrial membrane into the intermembrane space. These mt-hsp70-independent effects appear to be exerted at the level of the inner membrane through an interaction of the hydrophobic core of the sorting signal with component(s) of the translocase of the inner membrane. Hydrophobic sorting signals of inner membrane proteins inserted into the membrane from the matrix, as well as those of intermembrane space proteins, are capable of causing this mt-hsp70-independent stabilization, demonstrating that this phenomenon is not unique to those preproteins normally sorted to the intermembrane space.
Gruhler
A
A
Institut für Physiologische Chemie, Universität München, Goethestrasse 33, 80336 München, Federal Republic of Germany.
Arnold
I
I
Seytter
T
T
Guiard
B
B
Schwarz
E
E
Neupert
W
W
Stuart
R A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005656:Fungal Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D008666:Metalloendopeptidases / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008958:Models, Molecular; D011498:Protein Precursors / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D000096122:Mitochondrial Processing Peptidase
D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008666:Metalloendopeptidases; D008727:Methotrexate; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; D013762:Tetrahydrofolate Dehydrogenase; D000096122:Mitochondrial Processing Peptidase; C102549:TIM22 protein, S cerevisiae; C077016:TIM44 protein, S cerevisiae