The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex.

TitleThe essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex.
Publication TypeJournal Article
Year of Publication2001
AuthorsMurphy, MP, Leuenberger, D, Curran, SP, Oppliger, W, Koehler, CM
JournalMol Cell Biol
Date Published2001 Sep
KeywordsBiological Transport, Carrier Proteins, Fungal Proteins, Membrane Proteins, Membrane Transport Proteins, Mitochondria, Mitochondrial Membrane Transport Proteins, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction

The TIM22 protein import pathway of the yeast mitochondrion contains several components, including a family of five proteins (Tim8p, -9p, -10p, -12p, and -13p [Tim, for translocase of inner membrane]) that are located in the intermembrane space and are 25% identical. Tim9p and Tim10p have dual roles in mediating the import of inner membrane proteins. Like the Tim8p-Tim13p complex, the Tim9p-Tim10p complex functions as a putative chaperone to guide hydrophobic precursors across the intermembrane space. Like membrane-associated Tim12p, they are members of the Tim18p-Tim22p-Tim54p membrane complex that mediates precursor insertion into the membrane. To understand the role of this family in protein import, we have used a genetic approach to manipulate the complement of the small Tim proteins. A strain has been constructed that lacks the 70-kDa soluble Tim8p-Tim13p and Tim9p-Tim10p complexes in the intermembrane space. Instead, a functional version of Tim9p (Tim9(S67C)p), identified as a second-site suppressor of a conditional tim10 mutant, maintains viability. Characterization of this strain revealed that Tim9(S67C)p and Tim10p were tightly associated with the inner membrane, the soluble 70-kDa Tim8p-Tim13p and Tim9p-Tim10p complexes were not detectable, and the rate of protein import into isolated mitochondria proceeded at a slower rate. An arrested translocation intermediate bound to Tim9(S67C)p was located in the intermembrane space, associated with the inner membrane. We suggest that the 70-kDa complexes facilitate import, similar to the outer membrane receptors of the TOM (hetero-oligomeric translocase of the outer membrane) complex, and the essential role of Tim9p and Tim10p may be to mediate protein insertion in the inner membrane with the TIM22 complex.

Alternate JournalMol. Cell. Biol.
Citation Key10.1128/mcb.21.18.6132-6138.2001
PubMed ID11509656
PubMed Central IDPMC87330
Grant ListR01 GM061721 / GM / NIGMS NIH HHS / United States
1R01GM61721-01 / GM / NIGMS NIH HHS / United States