Disease relevance of TIM9

• We report here that Tim9 and Tim10 purified from Escherichia coli can form a complex of the same size as the endogenous complex from yeast mitochondria [1].

High impact information on TIM9

• Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10 [2].
• The soluble Tim9p-Tim10p (Tim, translocase of inner membrane) complex of the mitochondrial intermembrane space mediates the import of the carrier proteins and is a component of the TIM22 import system [3].
• Tim9, an essential protein of Saccharomyces cerevisiae, shares sequence similarity with Tim10 and Tim12 [4].
• Tim9, a new component of the TIM22.54 translocase in mitochondria [4].
• The patterns of binding sites on the substrate proteins suggest a mechanism by which portions of membrane-spanning segments together with flanking hydrophilic segments are recognized and bound by the Tim9/Tim10 complex as they emerge from the TOM complex into the intermembrane space [5].

Biological context of TIM9

• TIM9 has been identified as an additional novel gene required for the petite-positive phenotype in Saccharomyces cerevisiae. tim9-1 was obtained through a screen for respiratory-deficient strains that are unable to survive in the absence of mitochondrial DNA [6].
• The mitochondrial intermembrane space contains a protein complex essential for cell viability, the Tim9-Tim10 complex [7].
• MS/MS sequencing of these proteins identified them as plant homologues of the yeast zinc-finger carrier import components Tim9 and Tim10 [8].

Anatomical context of TIM9

• Tim9 and Tim10 are essential components of the "small Tim" family of proteins that facilitate insertion of polytopic proteins at the inner mitochondrial membrane [9].
• Reconstituted TOM core complex and Tim9/Tim10 complex of mitochondria are sufficient for translocation of the ADP/ATP carrier across membranes [5].

Associations of TIM9 with chemical compounds

• The mechanism by which the Tim9p-Tim10p complex assembles and binds the carriers is not well understood, but previous studies have proposed that the conserved cysteine residues in the 'twin CX3C' motif coordinate zinc and potentially generate a zinc-finger-like structure that binds to the matrix loops of the carrier proteins [3].
• The oxidized Tim10 generated in the presence of glutathione is competent for complex formation with its partner protein Tim9, confirming it has a native fold [10].

Physical interactions of TIM9

• The purified TOM core complex was reconstituted into lipid vesicles in which purified Tim9/Tim10 complex was entrapped [5].

Other interactions of TIM9

• Therefore, our results suggest that the Tim9p-Tim10p complex plays a key role in Tim23p import [11].
• Transcription of TIM9, a new factor required for the petite-positive phenotype of Saccharomyces cerevisiae, is defective in spt7 mutants [6].
• Deletion of Tim18p decreases the growth rate of yeast cells by a factor of two and is synthetically lethal with temperature-sensitive mutations in Tim9p or Tim10p [12].

References