title: Tim18p is a new component of the Tim54p-Tim22p translocon in the mitochondrial inner membrane.
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.
authors.affiliation: Department of Cell Biology and Anatomy, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: O
authors.initials: O
authors.lastname: Kerscher
authors.forename: N B
authors.initials: NB
authors.lastname: Sepuri
authors.forename: R E
authors.initials: RE
authors.lastname: Jensen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D017920:Antiporters; D002352:Carrier Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C102549:TIM22 protein, S cerevisiae; C110036:TIM54 protein, S cerevisiae; C403803:Tim18 protein, S cerevisiae; D006836:Hydro-Lyases; C021434:imidazoleglycerolphosphate dehydratase