High impact information on MAS6

• Tim21 is specific for a TIM23 form that cooperates with TOM and promotes inner membrane insertion [1].
• The presequence translocase of the inner mitochondrial membrane (TIM23 complex) operates at a central junction of protein import [1].
• Tim50 interacts with preproteins in transit and directs them to the channel protein Tim23 [2].
• By the simultaneous integration into two membranes, Tim23 forms contacts between the outer and inner mitochondrial membranes [3].
• Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria [4].

Biological context of MAS6

• In the absence of an inner membrane potential, Tim23p is translocated across the mitochondrial outer membrane, but not inserted into the inner membrane [5].
• To determine how the Tim23 protein itself is transported into mitochondria, we used chemical cross-linking to identify proteins adjacent to Tim23p during its biogenesis [5].
• One of the tom40 mutants, tom40-97, carries a single point mutation (W(243)R) resulting in an ineffective transfer of precursors to the TIM23 complex [6].
• Mitochondria from cells depleted of Tim50 displayed strongly reduced import kinetics of preproteins using the TIM23 complex [7].
• All subunits of the TIM23 translocase but one are essential for yeast cell viability [8].

Anatomical context of MAS6

• Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria [5].
• Tim23 import intermediates could also be cross-linked to the complex, suggesting a dual role for the Tim8-Tim13 intermembrane space complex in the import of proteins found in both the outer and inner mitochondrial membranes [9].
• Tim23p is a mitochondrial inner membrane protein essential for the import of proteins from the cytosol [10].

Associations of MAS6 with chemical compounds

• In contrast to precursors with an NH2-terminal targeting presequence that are imported in a linear NH2-terminal manner, we show that Tim23p crosses the outer membrane as a loop before inserting into the inner membrane [11].

Physical interactions of MAS6

• We suggest that Tim50 plays a crucial role in the transfer of preproteins from the TOM complex to the TIM23 complex through the intermembrane space [7].
• In particular, import of nuclear-encoded precursor proteins into and across the mitochondrial inner membrane is mediated by two distinct translocases, the TIM23 complex and the TIM22 complex [12].
• Although Tam41 is not a constituent of the TIM23 complex, depletion of Tam41 led to a decreased molecular size of the TIM23 complex and partial aggregation of Pam18 and -16 [13].
• Characterization of the mitochondrial inner membrane translocase complex: the Tim23p hydrophobic domain interacts with Tim17p but not with other Tim23p molecules [10].
• The purified C-terminal domain of Tim21 appears not to bind to any of the TIM23 components but rather specifically interacts with the TOM complex [14].

Regulatory relationships of MAS6

• On the basis of these observations we propose that charged residues in Tim17 are critical for the preprotein-induced gating of the TIM23 translocase [15].

Other interactions of MAS6

• Precursor proteins carrying amino-terminal targeting signals are translocated into the matrix by the integral inner membrane proteins Tim23 and Tim17 in cooperation with Tim44 and mitochondrial Hsp70 [16].
• We now show that the two 70 kDa complexes each mediate the import of a different subset of integral inner membrane proteins and that they can transfer these proteins to one of three different membrane insertion sites: the TIM22 complex, the TIM23 complex or an as yet uncharacterized insertion site [17].
• Tim18p does not cofractionate with the TIM23 complex upon immunoprecipitation or nondenaturing gel electrophoresis [18].
• Conserved N-terminal negative charges in the Tim17 subunit of the TIM23 translocase play a critical role in the import of preproteins into mitochondria [15].
• PiC thus appears to have a latent signal for sorting to the TIM23 pathway, which is exposed by reduced interactions with the Tim9-Tim10 complex and maintenance of the import competence [19].

Analytical, diagnostic and therapeutic context of MAS6

• TOM and TIM23 are the protein translocation channels of the mitochondrial outer and inner membranes, respectively, and their single channel behaviors at various pHs were determined using patch-clamp techniques [20].

References