Disease relevance of TOM70

• Given the role of the homologous Tom70 gene, the alteration of KIAA0719 expression may contribute to the changes in mitochondrial morphology and physiology caused by hypothyroidism in the developing rat brain [1].
• The cytosolic domain of yeast MOM72 was purified after expression in Escherichia coli as a homogeneous monomeric protein [2].

High impact information on TOM70

• Disruption of the chaperone/Tom70 recognition inhibits the import of these preproteins into mitochondria [3].
• Here, we show that in mammals, the cytosolic chaperones Hsp90 and Hsp70 dock onto a specialized TPR domain in the import receptor Tom70 at the outer mitochondrial membrane [3].
• We show that the precursor-MSF complex first binds to the Mas37p/Mas70p subunits of the mitochondrial import receptor [4].
• We have isolated the TOM core complex of Neurospora crassa by removing the receptors Tom70 and Tom20 from the isolated TOM holo complex by treatment with the detergent dodecyl maltoside [5].
• The Tom70 domain only bound the precursor in the presence of MSF, yielding a precursor-MSF-Tom70 complex; ATP hydrolysis by MSF released MSF and generated a precursor-Tom70 complex whose formation was inhibited by an excess of a functional presequence peptide, but not by 150 mM NaCl [6].

Biological context of TOM70

• These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis [7].
• The protein Tom71 is encoded by the open reading frame YHR117w (yeast chromosome VIII) and shares 53% amino acid sequence identity with Tom70, a protein import receptor of the mitochondrial outer membrane [8].
• The additional function of the TOM complex channel is probably facilitated by the upregulation of nuclear-encoded components of the TOM complex as has been shown for Tom40 (a major component of the channel) and Tom70 (one of the surface receptors) [9].
• Overexpression of Mom22 even suppressed the lethal phenotype of a double deletion of the two import receptors known so far (mom19 delta mom72 delta) [10].
• Inactivation of the Neurospora crassa mitochondrial outer membrane protein TOM70 by repeat-induced point mutation (RIP) causes defects in mitochondrial protein import and morphology [11].

Anatomical context of TOM70

• The reciprocal situation was found for protein import into delta MOM72 mitochondria [12].
• Like Tom70, Tom71 is anchored to the mitochondrial outer membrane via its N terminus, thereby exposing a large C-terminal domain to the cytosol [8].
• Immunohistochemical analysis using these antisera revealed that in the otoliths of adult fish, OMP-1 and otolin-1 were colocalized along the daily rings possibly formed by alternate deposition of calcium carbonate and organic matrices [13].
• In the adult inner ear, OMP-1 was produced at most of the saccular epithelium, while otolin-1 was produced at a limited part of cylindrical cells located at the marginal zone of the sensory epithelium [13].

Associations of TOM70 with chemical compounds

• Yeast Mas70p and NADH cytochrome b5 reductase are bitopic integral proteins of the mitochondrial outer membrane and are inserted into the lipid-bilayer in an Nin-Ccyto orientation via an NH2-terminal signal-anchor sequence [14].
• Mas70p had no effect on the binding or the import of artificial precursors containing mouse dihydrofolate as the "mature" domain [15].
• Mas70p also enhanced the direct import of pre-alcohol dehydrogenase III into isolated mitochondria, provided the precursor was first denatured with urea [15].

Physical interactions of TOM70

• A yeast mutant lacking both Tom20 and Tom70 can still form the GIP complex when sufficient amounts of Tom22 are synthesized [16].
• The Mas20p and Mas70p subunits of the protein import receptor of yeast mitochondria interact via the tetratricopeptide repeat motif in Mas20p: evidence for a single hetero-oligomeric receptor [17].

Other interactions of TOM70

• (ii) Tom20 and Tom70 are not essential for the generation of the GIP complex [16].
• Overproduction of PDR3 suppresses mitochondrial import defects associated with a TOM70 null mutation by increasing the expression of TOM72 in Saccharomyces cerevisiae [7].
• Consequently, it may be concluded that depletion of the VDAC channel might influence differentially the expression of TOM40 and TOM70 genes [9].
• Preproteins with internal signals such as inner membrane carriers use Tom70, the GIP complex, and the special Tim pathway, involving small Tims of the intermembrane space and Tim22-Tim54 of the inner membrane [18].
• The positively charged amino-terminal region of Tim54 is required for membrane translocation but not for targeting to Tom70 [18].

Analytical, diagnostic and therapeutic context of TOM70

• Genome sequence analyses suggest no Tom70 receptor subunit exists in plants or protozoans, raising questions about its ancestry, function and the importance of its activity [19].

References