Disease relevance of Mtx1

• In this study, transient transfection of rat chondrosarcoma cells and NIH-3T3 fibroblasts demonstrated that Thbs3 is regulated in a cell type-specific manner by a position- and orientation-independent far upstream enhancer located within intron 6 of Mtx [1].
• At doses active on the DH models and on carrageenin inflammation, Cy induced a lasting blood leukopenia, but CsA and Mtx did not [2].
• Of the immunosuppressants, CsA reduced all the DH reactions while Aza mainly reduced the reaction to SRBC; Cy and Mtx were mainly active on SBRC and MBSA inflammations [2].
• On another hand CsA, Cy and Mtx were inactive on the 3-h phase but decreased the 24-h phase of carrageenin edema [2].

High impact information on Mtx1

• Despite its greater proximity to the transcription start site of Mtx, the Thbs3 enhancer did not have a significant effect on Mtx expression [1].
• Thus, despite their close proximity, the genes of the Mtx/Thbs3 gene cluster are regulated independently [1].
• Mouse Thbs3 is located just downstream from the divergently transcribed metaxin gene (Mtx), which encodes an outer mitochondrial membrane import protein [1].
• Antibodies against metaxin, when preincubated with mitochondria, partially inhibited the uptake of radiolabeled preadrenodoxin into mitochondria [3].
• The characterization of metaxin provides an opportunity to elucidate similarities and possible differences in the mechanisms of protein import between fungi and mammals and in the phenotypes of fungi and mammals lacking mitochondrial import receptors [3].

Biological context of Mtx1

• A far upstream, cell type-specific enhancer of the mouse thrombospondin 3 gene is located within intron 6 of the adjacent metaxin gene [1].
• Metaxin is therefore the second mammalian component of the protein translocation apparatus of the mitochondrial outer membrane to be characterized at the molecular level and the first for which an inherited mutation has been described [3].
• Like many genes regulated by a TATA-less promoter, the transcription start site of metaxin is heterogeneous [4].
• Thus, despite the potential for common regulatory mechanisms, the available evidence indicates that the Mtx minimal promoter does not significantly affect Thbs3 gene expression [4].
• Finally, the up-regulation of a differentially expressed gene (metaxin) mediated by its promoter was evaluated in a functional assay [5].

Anatomical context of Mtx1

• In addition, metaxin was highly susceptible to proteases in intact mitochondria [3].
• We therefore conclude that metaxin is a mitochondrial protein that extends into the cytosol while anchored into the outer membrane at its C terminus [3].
• When metaxin cDNA was transfected into COS cells, immunofluorescence staining demonstrated that the protein is located in mitochondria [3].
• When treated with doxorubicin, somatic cells transfected with a genetic construct including the promoter of metaxin and a reporter gene showed increases in expression similar to those observed in fetal oocytes [5].
• High-titer DHFR virus (10(7) colony-forming units/ml) was generated by gene amplification adapting virus-producer cell lines to grow in medium containing increasing concentrations of Mtx [6].

Other interactions of Mtx1

• Deletion of the four upstream Sp1-binding elements, on the other hand, demonstrated that these motifs are superfluous in context of the larger Mtx promoter [4].
• Another targeted modification in the murine glucocerebrosidase gene locus led to the discovery of a contiguous gene, metaxin [7].
• The early embryonic lethal phenotype of mice lacking metaxin demonstrates that efficient import of proteins into mitochondria is crucial for cellular survival [3].

References