Disease relevance of IMMT

• Immunofluorescence microscopy, fractionating of human osteosarcoma cells, and protease protection experiments with isolated mitochondria and mitoplasts indicate that mitofilin is an integral membrane protein of the inner mitochondrial membrane [1].
• Manifold decreased protein levels of matrin 3, reduced motor protein HMP and hlark in fetal Down's syndrome brain [2].
• Sixty-one human myeloma proteins (HMP) from patients with multiple myeloma and Waldenström macroglobulinemia were tested for anti-idiotypic (Id) activity against autoantibodies to double-stranded DNA, small nuclear ribonucleoproteins, and human thyroglobulin (HTg), by competitive radioimmunoassays and enzyme immunoassays [3].
• In particular, we assign the thiamin transporter function to yuaJ in the Bacillus/Clostridium group and the HMP transporter function to an ABC transporter thiXYZ in some proteobacteria and firmicutes [4].
• OBJECTIVE: To determine prevalence of HIV infection and risk behaviours among male inmates of Her Majesty's Prison (HMP) Barlinnie, Glasgow, Scotland on 8-9 September 1994 [5].

Psychiatry related information on IMMT

• HMP Whitemoor, Cambridgeshire, is currently piloting a programme for the assessment and treatment of severe personality disorders [6].
• BACKGROUND: The aim of this study is to evaluate the value ofTc-99 HMP AO cerebral SPECT imaging to confirm brain death in patients with complex spinal automatism [7].

High impact information on IMMT

• The CO2 generated by the HMP shunt is spontaneously hydrated and the protons (H+) are secreted upon the dissociation of carbonic acid [8].
• Reaction of human neutrophils with aggregated immunoglobulin on nonphagocytosable surfaces results in secretion of granule enzymes (exocytosis of granules) and stimulation of glucose oxidation by the nexose monophosphate pathway (HMP) [9].
• Aggregated immunoglobulin reacting with neutrophil Fc receptors thus induces both degranulation (exocytosis) and increased HMP activity [9].
• (b) Removal of Ca++ and addition of agents which increased the intracellular levels of cyclic AMP (cAMP), however, prevented both activities, while colchicine had greater inhibitory activity on HMP stimulation than upon secretion [9].
• It was found that (a) HMP stimulation could be selectively inhibited under conditions where release of granule enzymes remained unchanged or was enhanced, for example, by reduced glucose concentration or by 2-deoxyglucose [9].

Chemical compound and disease context of IMMT

• LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high- molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP [10].

Biological context of IMMT

• Amino acid sequences of peptides produced by limited proteolysis of each protein in the spots from the strains were identical or highly homologous to those of mitofilin, a mitochondrial inner membrane protein (IMMT) in humans [11].
• Although metabolic flux increased due to mitofilin deficiency, mitochondrial oxidative phosphorylation was not increased accordingly [12].
• Down-regulation of mitofilin in HeLa cells by using specific small interfering RNA lead to decreased cellular proliferation and increased apoptosis, suggesting abnormal mitochondrial function [12].
• Using reverse PCR, we provide evidence that both isoforms are derived by alternative splicing and encode two proteins of 88 and 90 kDa that are detected in immunoblot analyses with mitofilin-specific antibodies [1].
• 35S-labeled mitofilin is transported into isolated yeast mitochondria in a reaction that depends on the membrane potential across the inner mitochondrial membrane (delta psi) [1].

Anatomical context of IMMT

• Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex [12].
• Mitofilin is a transmembrane protein of the inner mitochondrial membrane expressed as two isoforms [1].
• Mitofilin, also known as heart muscle protein, is a recently identified mitochondrial protein [1].
• The nuclear matrix protein matrin 3, cytoskeletal motor protein HMP, and the circadian clock protein hlark were significantly decreased in fetal DS brain [2].
• The role of HMP stimulation in the enzyme secretion and some requirements for the two neutrophil activities have been examined [9].

Associations of IMMT with chemical compounds

• We find that, at biologically relevant O(2) concentrations, HMP preferentially binds NO (not O(2)), which it then reacts with oxygen to form nitrate (in essence NO(-) + O(2) --> NO(3)(-)) [13].
• It has been alternatively suggested that HMP activity is inhibited at low pO(2) because the enzyme is then in the relatively inactive nitrosyl form [k(off)/k(on) for NO (0.000008 microM) k(off)/k(on) for O(2) (0.012 microM) and K(M) for O(2) = 30-100 microM] [13].
• Based on analysis of co-occurrence of the thiamin biosynthetic genes in complete genomes, we predict that eubacteria, archaea, and eukaryota have different pathways for the HMP and hydroxyethylthiazole biosynthesis [4].
• A previously undescribed high molecular mass protein (HMP) from human erythrocyte membranes was solubilized by Triton X-100 and purified on a calmodulin-agarose column in the presence of Ca2+ [14].
• Vitamin B(1) in its active form thiamin pyrophosphate is an essential coenzyme that is synthesized by coupling of pyrimidine (hydroxymethylpyrimidine; HMP) and thiazole (hydroxyethylthiazole) moieties in bacteria [4].

Physical interactions of IMMT

• Oxa1p is a mitochondrial inner membrane protein that is mainly required for the insertion/assembly of complex IV and ATP synthase and is functionally conserved in yeasts, humans, and plants [15].

Other interactions of IMMT

• BCS1L, a mitochondrial inner-membrane protein, is a chaperone necessary for the assembly of mitochondrial respiratory chain complex III [16].
• Uncoupling protein-1 (UCP1) is a brown fat-specific mitochondrial inner membrane protein with proton transport activity [17].
• The recently discovered uncoupling protein 3 (UCP3) is highly homologous to the mitochondrial inner membrane protein UCP1, which generates heat by uncoupling the respiratory chain from oxidative phosphorylation [18].
• Vpr binds to the adenine nucleotide translocator (ANT), a mitochondrial inner membrane protein which also interacts with apoptosis-regulatory proteins from the Bcl-2/Bax family [19].
• Amish lethal microcephaly maps to 17q25 and may be caused by a defect in a mitochondrial inner membrane protein functioning as a 2-ketoglutarate transporter [20].

Analytical, diagnostic and therapeutic context of IMMT

• Sequence analysis and our results suggest that mitofilin is anchored in the inner mitochondrial membrane with an amino-terminal transmembrane domain, while the majority of the protein is extruding into the intermembrane space [1].
• HMP was found to cross-react in Western blots with an antibody raised against the rabbit multicatalytic proteinase [14].
• These results show that oral administration of HMP preferentially induces exclusive Th2-type immune responses, which may prevent the development of HMP (S-IgA and Lf)-specific mucosally induced tolerance [21].
• Gel filtration column chromatography indicated that the native protein exists as a dimer, while isoelectric focusing suggested that there were at least four HMP isotypes [22].
• Similarly, in RBC of different ages, obtained by density gradient ultracentrifugation, the glucose-6-phosphate concentration range from 57 (young cells) to 18 (old cells) nmole/ml RBC but the rate at which glucose is utilized in the HMP is unchanged [23].

References