MTFMT encodes the nuclear-encoded mitochondrial methionyl-tRNA formyltransferase. Metazoan mitochondria use a single tRNA(Met) for both initiation and elongation; MTFMT transfers a formyl group from 10-formyltetrahydrofolate to part of the aminoacylated Met-tRNA(Met) pool, generating fMet-tRNA(Met), which is preferred by the mitochondrial initiation factor for translation initiation on mitochondrial ribosomes. Formylation is required for efficient synthesis of the mtDNA-encoded respiratory-chain subunits in human cells, and biallelic loss-of-function or hypomorphic variants cause Leigh syndrome with combined oxidative phosphorylation deficiency (COXPD15) or isolated complex I deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: catalytic activity is a root-level MF term from an InterPro mapping. Reason: True of MTFMT but uninformative, because GO:0004479 methionyl-tRNA formyltransferase activity, accepted in this review on IBA and IDA rows, already entails it. GO:0004479 is a confirmed descendant of GO:0003824 in the QuickGO is_a closure. Supporting Evidence: PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. |
| GO:0004479 methionyl-tRNA formyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Methionyl-tRNA formyltransferase activity is the core catalytic function of MTFMT. Reason: Methionyl-tRNA formyltransferase activity is the core catalytic function of MTFMT. The IBA is consistent with direct biochemical assays of recombinant human mt-MTF and of patient variants, and with loss of fMet-tRNA(Met) in patient cells. Supporting Evidence: PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. PMID:25288793 The S125L mutant has 653-fold lower activity, whereas the S209L mutant has 36-fold lower activity. |
| GO:0004479 methionyl-tRNA formyltransferase activity | IDA PMID:25288793 Biochemical characterization of pathogenic mutations in huma... | ACCEPT | Summary: Direct biochemical characterization of recombinant human mitochondrial MTF and of the disease variants S125L and S209L, which reduce formyltransferase activity 653-fold and 36-fold. Reason: Direct biochemical characterization of recombinant human mitochondrial MTF and of the disease variants S125L and S209L, which reduce formyltransferase activity 653-fold and 36-fold. This is the core MF of MTFMT. Supporting Evidence: PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. PMID:25288793 The S125L mutant has 653-fold lower activity, whereas the S209L mutant has 36-fold lower activity. |
| GO:0004479 methionyl-tRNA formyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The combined IEA (RHEA:24380 / EC 2.1.2.9) agrees with experimental data; methionyl-tRNA formyltransferase activity is the core MF. Reason: The combined IEA (RHEA:24380 / EC 2.1.2.9) agrees with experimental data; methionyl-tRNA formyltransferase activity is the core MF. Supporting Evidence: PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion is supported by the MitoCoP high-confidence mitochondrial proteome. Reason: Mitochondrion is supported by the MitoCoP high-confidence mitochondrial proteome. MTFMT is the mitochondrial methionyl-tRNA formyltransferase; it acts on the mitochondrial Met-tRNA(Met) pool, so mitochondrial (matrix) localization is expected and well supported. Supporting Evidence: PMID:34800366 We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:21907147 A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA for mitochondrion is consistent with the organelle-specific function of MTFMT in formylating mitochondrial initiator Met-tRNA(Met). Reason: The IBA for mitochondrion is consistent with the organelle-specific function of MTFMT in formylating mitochondrial initiator Met-tRNA(Met). Supporting Evidence: PMID:21907147 A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrion from the UniProt subcellular-location mapping is correct. Reason: Mitochondrion from the UniProt subcellular-location mapping is correct. MTFMT is the mitochondrial methionyl-tRNA formyltransferase; it acts on the mitochondrial Met-tRNA(Met) pool, so mitochondrial (matrix) localization is expected and well supported. Supporting Evidence: PMID:21907147 A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrion transferred by sequence similarity from bovine MTF is correct and consistent with the human functional data. Reason: Mitochondrion transferred by sequence similarity from bovine MTF is correct and consistent with the human functional data. MTFMT is the mitochondrial methionyl-tRNA formyltransferase; it acts on the mitochondrial Met-tRNA(Met) pool, so mitochondrial (matrix) localization is expected and well supported. Supporting Evidence: PMID:21907147 A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation |
| GO:0006413 translational initiation | IEA GO_REF:0000108 | MODIFY | Summary: Translational initiation is inferred from the MF via an inter-ontology link. Reason: Translational initiation is inferred from the MF via an inter-ontology link. The fMet-tRNA(Met) that MTFMT generates is used specifically by the mitochondrial initiation machinery, and loss of MTFMT impairs mitochondrial translation. The more precise term is mitochondrial translational initiation (GO:0070124). Proposed replacements: mitochondrial translational initiation Supporting Evidence: PMID:21907147 A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation PMID:21907147 Patient fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of MTFMT. |
| GO:0071951 conversion of methionyl-tRNA to N-formyl-methionyl-tRNA | IBA GO_REF:0000033 | ACCEPT | Summary: Conversion of methionyl-tRNA to N-formyl-methionyl-tRNA is the BP directly carried out by the MTFMT reaction, and is shown experimentally in human cells and with purified enzyme. Reason: Conversion of methionyl-tRNA to N-formyl-methionyl-tRNA is the BP directly carried out by the MTFMT reaction, and is shown experimentally in human cells and with purified enzyme. Supporting Evidence: PMID:21907147 patient fibroblasts have dramatically reduced fMet-tRNA(Met) levels and an abnormal formylation profile of mitochondrially translated COX1 PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. |
| GO:0071951 conversion of methionyl-tRNA to N-formyl-methionyl-tRNA | IDA PMID:25288793 Biochemical characterization of pathogenic mutations in huma... | ACCEPT | Summary: The purified human enzyme formylates Met-tRNA(Met); this process term is the direct consequence of the core MF. Reason: The purified human enzyme formylates Met-tRNA(Met); this process term is the direct consequence of the core MF. Supporting Evidence: PMID:25288793 N-Formylation of initiator methionyl-tRNA (Met-tRNA(Met)) by methionyl-tRNA formyltransferase (MTF) is important for translation initiation in bacteria, mitochondria, and chloroplasts. PMID:25288793 The S125L mutant has 653-fold lower activity, whereas the S209L mutant has 36-fold lower activity. |
| GO:0071951 conversion of methionyl-tRNA to N-formyl-methionyl-tRNA | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro-based IEA agrees with experimental evidence for formylation of mitochondrial Met-tRNA(Met) by MTFMT. Reason: The InterPro-based IEA agrees with experimental evidence for formylation of mitochondrial Met-tRNA(Met) by MTFMT. Supporting Evidence: PMID:21907147 patient fibroblasts have dramatically reduced fMet-tRNA(Met) levels and an abnormal formylation profile of mitochondrially translated COX1 |
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Download this section (compressed HTML)Q: What fraction of the mitochondrial Met-tRNA(Met) pool must be formylated to sustain normal mitochondrial translation initiation in different human tissues, and why is the brain particularly sensitive to its reduction?
Q: Does reduced formylation alter the N-terminal formylation state of individual mtDNA-encoded proteins differently, and does that affect their assembly into respiratory-chain complexes?
Experiment: Quantify formylated versus non-formylated Met-tRNA(Met) and mitoribosome-profiling initiation density for all 13 mtDNA-encoded ORFs in isogenic MTFMT-null and c.626C>T knock-in human iPSC-derived neurons.
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