Abstract
The mitochondrial inner membrane contains two separate translocons: one required for the translocation of matrix-targeted proteins (the Tim23p-Tim17p complex) and one for the insertion of polytopic proteins into the mitochondrial inner membrane (the Tim54p-Tim22p complex). To identify new members of the Tim54p-Tim22p complex, we screened for high-copy suppressors of the temperature-sensitive tim54-1 mutant. We identified a new gene, TIM18, that encodes an integral protein of the inner membrane. The following genetic and biochemical observations suggest that the Tim18 protein is part of the Tim54p-Tim22p complex in the inner membrane: multiple copies of TIM18 suppress the tim54-1 growth defect; the tim18::HIS3 disruption is synthetically lethal with tim54-1; Tim54p and Tim22p can be coimmune precipitated with the Tim18 protein; and Tim18p, along with Tim54p and Tim22p, is detected in an approximately 300-kDa complex after blue native electrophoresis. We propose that Tim18p is a new component of the Tim54p-Tim22p machinery that facilitates insertion of polytopic proteins into the mitochondrial inner membrane.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antiporters*
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Base Sequence
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Binding Sites
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Biological Transport
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Division
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Hydro-Lyases / genetics
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Hydro-Lyases / metabolism
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Intracellular Membranes / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Membrane Transport Proteins*
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Mitochondria / metabolism*
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Mitochondrial Membrane Transport Proteins*
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Mitochondrial Precursor Protein Import Complex Proteins
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Molecular Sequence Data
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Rabbits
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
Substances
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Antiporters
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Carrier Proteins
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Fungal Proteins
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Membrane Proteins
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Membrane Transport Proteins
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Mitochondrial Membrane Transport Proteins
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Mitochondrial Precursor Protein Import Complex Proteins
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Saccharomyces cerevisiae Proteins
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TIM22 protein, S cerevisiae
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TIM54 protein, S cerevisiae
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Tim18 protein, S cerevisiae
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Hydro-Lyases
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imidazoleglycerolphosphate dehydratase