High impact information on TOM22

• The single membrane anchor of Tom22 is required for a stable interaction between the core complexes, whereas its cytosolic domain serves as docking point for the peripheral receptors Tom20 and Tom70 [1].
• The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 (refs 11-13) [1].
• Thus, Tim50 functions as a dynamic factor and the IMS domain of Tom22 represents a stabilizing element in formation of a productive translocation contact site supercomplex [2].
• To test this 'acid chain' hypothesis, we assayed the interaction of mitochondrial precursors with three acidic receptor domains: the cytosolic domain of Tom20 and the intermembrane space domain of Tom22 and Tim23 [3].
• If this Mas22p domain is deleted, respiration-driven growth of the cells is compromised and import of different precursors into isolated mitochondria is inhibited 3- to 8-fold [4].

Biological context of TOM22

• The mitochondrial receptor complex: Mom22 is essential for cell viability and directly interacts with preproteins [5].
• Mitochondria lacking the central receptor and organizing protein Tom22 contain greatly reduced levels of cytochrome c. We conclude that up to two components of the TOM complex, Tom22 and possibly the GIP, are involved in the biogenesis of cytochrome c [6].
• The trans domain from the Arabidopsis thaliana protein functions in yeast lacking their own Tom22 by complementing protein import defects and restoring cell growth [7].
• TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax [8].
• In yeast, a haploid strain for TOM22 exhibited a decreased expression of TOM22 and mitochondrial association of ectopically expressed human Bax [8].

Anatomical context of TOM22

• Role of the negative charges in the cytosolic domain of TOM22 in the import of precursor proteins into mitochondria [9].
• The amino-terminal 84 amino acids of TOM22 extend into the cytosol and include 19 negatively and 6 positively charged residues [9].
• TOM22 is an essential mitochondrial outer membrane protein required for the import of precursor proteins into the organelles [9].
• Protein import channel of the outer mitochondrial membrane: a highly stable Tom40-Tom22 core structure differentially interacts with preproteins, small tom proteins, and import receptors [10].

Physical interactions of TOM22

• In addition, Tom6 was observed to interact with Tom22 in a manner that depends on the presence of preproteins in transit [11].

Regulatory relationships of TOM22

• Tom6 is required to promote but not to maintain a stable association between Tom22 and Tom40 [12].
• The Tom40 assembly is influenced by a block of negatively charged amino acid residues in the cytosolic domain of Tom22, indicating a cross-talk between preprotein receptors and the translocation pore [13].

Other interactions of TOM22

• Maturation to the 400 kDa complex occurs by association of Tom7 and Tom22 [14].
• (iii) Tom6 functions as an assembly factor for Tom22, promoting its stable association with Tom40 [12].
• The intermembrane space domain of the receptor Tom22 supports the stabilization of the Oxa1 intermediate [15].
• A chemically synthesized presequence peptide competes with preproteins for binding to Tom20 and Tom22 but not to Tom70 [16].

Analytical, diagnostic and therapeutic context of TOM22

• Peptide mapping showed that the interaction of Bax with TOM22 involved the first alpha helix of Bax and possibly two central alpha helices, which are homologous to the pore forming domains of some toxins [8].
• By using a bacterial two-hybrid assay and crosslinking strategies, we have identified TOM22, a component of the translocase of the outer mitochondrial membrane (TOM), as a mitochondrial receptor of Bax [8].

References