Disease relevance of MTCH2

• We have recently shown that Mimp, a mitochondrial carrier protein homologue, is induced by Met-hepatocyte growth factor/scatter factor (HGF/SF) signaling and decreases the mitochondrial membrane potential in DA3 mammary adenocarcinoma cells [1].
• MIMP is under preclinical development for early HIV disease to forestall progression to AIDS by attenuating virus-induced immunosuppression [2].
• Furthermore, MIMP enhanced responses to Hepatitis B and influenza vaccines [3].
• Among these studies, MIMP displays protective effects in several in vivo models of infectious disease following administration by one of several routes including oral [3].

High impact information on MTCH2

• Our studies with mouse liver mitochondria indicate that Mtch2 is an integral membrane protein exposed on the surface of mitochondria [4].
• Induction of Mimp or its transient expression does not lead to apoptosis [1].
• Moreover, exogenous Mimp prevents the HGF/SF-induced transcription of the serum response element-luciferase reporter gene [1].
• Three of the four genes (mitochondrial carrier homolog 2, PIG11, and pRDI-BF1-rIZ1 domain containing 11) were uniformly expressed by an index panel of suppressed microcell hybrid cell lines, identifying them as candidate liver tumor suppressor genes [5].
• Methyl inosine monophosphate (MIMP) augments T-lymphocyte mitogen responses and reverses various immunosuppressants [6].

Chemical compound and disease context of MTCH2

• Methyl inosine monophosphate (MIMP), a new purine immunomodulator for HIV infection [7].

Biological context of MTCH2

• Mimp encodes a 33-kDa protein that shows sequence homology to the family of mitochondrial carrier proteins (MCPs) [8].
• Met-HGF/SF signal transduction induces mimp, a novel mitochondrial carrier homologue, which leads to mitochondrial depolarization [8].
• MIMP, but not IMP, is resistant to hydrolysis by 5'nucleotidase; thus, MIMP appears to be a protected analogue of IMP which is capable of in vivo action [6].

Anatomical context of MTCH2

• Using immunostaining for HA-tagged mMimp and a GFP-mMimp chimeric protein as well as subcellular fractionation, we determined that Mimp is primarily localized to the mitochondria [8].
• These data indicate that MIMP potentiates normal T-lymphocyte mitogen responses and restores those impaired by a variety of inflammatory and immunosuppressive influences [6].
• MIMP does not directly stimulate lymphocytes alone in the absence of mitogen [7].
• Methyl inosine monophosphate (MIMP) augments preferentially the in vitro responses of human and murine lymphocytes to a T-cell mitogen such as phytohemagglutinin (PHA) and inconsistently to a B-cell mitogen such as pokeweed or lipopolysaccharide (LPS) [6].
• Methyl inosine 5'-monophosphate (MIMP) was designed and synthesized in an endeavor to generate compounds with immunostimulatory activity based on the precedent of purines, particularly inosine playing a central role in the development and function of the immune system [3].

Associations of MTCH2 with chemical compounds

• Immunopharmacologic properties of inosine 5'-methyl monophosphate (MIMP) [9].
• MIMP is a new thymomimetic purine under development for immunorestorative therapy [2].
• In vivo experiments showed that MIMP significantly delayed death in a murine FLV AIDS model at a dose of 1 mg/kg by the oral or parenteral route [2].
• When PHA responses of human lymphocytes are suppressed in vitro by an HIV-derived immunosuppressive peptide, interferon alpha, or prostaglandin PGE2, MIMP (0.1-100 micrograms/ml) progressively restores the depressed response; however, when the suppression is severe (greater than 50%), MIMP cannot restore the response [6].
• The effect of 1 micrograms/ml MIMP was comparable with that observed with indomethacin (10(-6) M) and interleukin-2 (IL2 - 4 units/ml) and was additive with each of these stimulants [2].

References