Mitochondrial translation (Homo sapiens)

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2, 5, 10, 11, 14...111, 4, 6, 16, 18...7, 11, 1281311191, 3, 14, 15, 22147, 11, 12mitochondrial matrixMRPL24 MRPL41 MRPL51 MRPS11 MTRF1L MRPS24 MRPL11 MRPS23 MRPL18 MRPS18B MRPL50 Mitochondrial 16SrRNA MRPL20 PiMRPL10 MRPL22 MRPS6 MRPL50 MRPS15 MRPL1 MRPL40 MRPL42 MRPL39 CHCHD1 MRPL28 MRPL36 MRPL20 MRPL42 ICT1 CHCHD1 MRPL44 MRPS26 MRPL4 MRPS35 MRPS18B MRPL16 MRPS25 MRPL54 MRPS18A MRPL52 MRPS22 MRPL41 MRPS5 MRPS18C MRPL52 CHCHD1 MRPL23 MRPS11 MRPS27 ICT1 MRPS28 MRPS18A MRPL22 MRPL2 MRPS25 MRPL50 MRPS18B MRPL37 Mitochondrial 16SrRNA MRPS36 MRPL1 MRPL47 MRPL35 MRPL27 MRPS26 MRPL30 MRPS16 MRPL36 CHCHD1 MRPL9 MRPL50 MRPL13 MRPS26 MRPL35 MRPS22 MRPL54 MRPL15 MRPL9 Mitochondrial 12SrRNA MRPL55 MRPL36 TUFM GADD45GIP1 MRPL11 MRPL16 MRPL36 AURKAIP1 MRPL24 DAP3 MRPL19 MRPS25 MRPS11 PTCD3 MRPL2 MRPS14 MRPS27 MRPL2 MRPS30 PTCD3 MRPS31 MRPL34 MRPL17 MRPL16 ICT1 MRPL55 MRPS31 GTPMRPL23 MRPS12 MRPS12 GTP MRPS10 MRPL51 MRPL33 MRPS6 MRPS18B MRPS7 MRPS36 MRPL30 MRPS11 MRPL18 MRPL48 MRPL12 MRPS24 MRPL16 MRPL18 MRPS5 MRPL39 MRPS18A TUFM MRPL21 MRPL4 MRPL39 MRPS21 MRPL27 MRPL47 10-formyl-THFMRPS5 28Sribosomalsubunit:MTIF3:MTIF2:GTP:mRNA:fMet-tRNAGADD45GIP1 MRPL46 AURKAIP1 MRPS25 MRPL17 MRPL38 MRPS6 MRPS30 MRPS18A MRPL20 28S ribosomalsubunitMRPL10 MRPL15 MRPS21 MRPL40 MRPS6 MRPL17 MRPS33 CHCHD1 MRPS30 MRPS21 MRPS34 MRPL52 MRPL43 MRPS34 MRPL39 MRPS10 MRPS21 MRPS30 MRPL28 MRPS22 MRPL20 AURKAIP1 MRPL15 MRPS14 MRPS7 MRPL44 MRPL3 MRPS7 GFM1 DAP3 MRPS15 MRPL41 MRPS17 MRPL37 MRPL55 PiMRPL19 MRPL19 MRPL19 MRPL44 MRPL15 MRPS31 MRPL32 MRPS24 55Sribosome:mRNA:peptidyl-tRNA at P-siteMRPS24 AURKAIP1 MRPL50 MRPS15 MRPL35 DAP3 MRPS34 PTCD3 MRPS26 MRPL10 MRPS18C MRPL49 MRPL45 MRPS11 MRPL53 TUFM MRPL27 MRPL32 TUFM:GTPCHCHD1 MRPS16 MRPL13 MRPL27 MRPL47 MRPS18B MRPS15 MRPS17 MRPL22 MRPL1 MRPL38 MRPL3 MRPL24 MRPL9 MRPS18C MRPS25 GDPMRPS33 MRPS34 MRPS18C MRPS15 MRPL49 MRPL38 MRPL50 MRPL40 MRPS31 MRPL4 MRPS12 MRPS18C MRPS34 Mitochondrial 12SrRNA MRPS14 Mitochondrial 12SrRNA MRPS27 MRPS12 MRPL32 MRPS26 MRPL13 MRPL50 MRPL2 MTIF2MRPL11 DAP3 MRPL38 MRPL35 MTFMTMRPS6 MRPL22 MRPS9 MRPL13 MRPL47 MRPS18A MRPS35 MRPS9 GTP MRPL48 MRPL24 AURKAIP1 MRPL33 MRPS10 MRPL24 MRPL32 MRPS35 Mitochondrial 12SrRNA GDPMRPS5 MRPL4 Mitochondrial 16SrRNA MRPS17 MRPL4 MRPL44 MRPL37 MRPL42 MRPS12 MRPL34 MRPL2 MRPL10 MRPL40 MRPL50 PiMitochondrial 12SrRNA GTP MRPL27 MRPL21 MRPS30 MRPL36 MRPL33 MRPS26 aminoacyl-tRNAMRPS30 AURKAIP1 MRPL34 MRPS30 MRPS22 MRPL55 MRPL49 MRPL40 MRPL28 MRPL23 MRPL15 MRPL55 MRPL46 MRPL37 MRPS6 MRPS14 GTP MRPL10 MRPS31 MRPS28 MRPL47 MRPS7 MRPL9 MRPS16 55Sribosome:mRNA:tRNA:peptidyl-tRNA:GFM1:GTPICT1 MRPS34 MRPL46 MRPL38 MRPS11 MRPL18 MRPL28 MRPS18A MRPL13 MRPS31 MRPS16 MRPS27 MRPL12 MRPL39 MTIF2:GTPMRPL36 MRPS16 MRPL27 GFM2 MRPL47 GADD45GIP1 MRPL14 28S ribosomalsubunit:MTIF3MRPS9 MRPS31 MRPL46 MRPS21 MRPL13 MRPS15 MRPL49 MRPS22 MRPS17 MRRF MRPL53 MRPS10 MRPL46 MRPS26 MRPL34 MRPS26 MRPS18C GTPMRPL53 GFM2 MRPL33 TSFMMRPS18C MRPL36 MRPL28 MRPL2 MRPL35 CHCHD1 GADD45GIP1 MRPL10 MRPL30 DAP3 MRPL41 MRPL10 MRPS36 MRPL22 MRPL11 MRPS31 MRPL51 MRPL10 MRPS28 MRPL49 AURKAIP1 MRPL17 MRPS24 MRPS9 MRPL12 MRPL30 MRPL50 MRPL39 MRPS5 55Sribosome:mRNA:fMet-tRNAMRPL55 MRPL21 MRPL53 tRNA(Met)MRPL20 MRPL46 MRPS9 MRPS26 Mitochondrial 12SrRNA PiMRPL4 MRPS27 MRPL21 MRPL16 MRPL11 MRPS7 MRPL30 MRPS23 MRPL44 MRPS15 PTCD3 MRPL15 MRPS18A MRPL9 MRPL51 MRPS22 MRPL2 MRPL33 MRPL17 MRPS17 MRPL21 MRPL3 DAP3 MRPS10 ICT1 MRPS14 MRPL53 AURKAIP1 MRPL4 MRPS9 MTIF3 MRPL3 MRPL36 MRPL34 MRPL3 MRPS6 MRPS14 MRPL1 MRPS18C Mitochondrial 16SrRNA MRPL43 MRPS12 MRPL9 TSFM MRPL39 Mitochondrial 12SrRNA MRPS16 MRPL28 MRPS10 MRPL21 MRPL40 MRPL16 MRPS11 MRPL41 MRPS34 MRPL24 MRPS36 MRPL48 MRPL38 MRPL34 MRPS18C MRPS16 MRPL12 GADD45GIP1 Mitochondrial 12SrRNA ICT1 MRPL15 MRPL1 MRPL53 MRPL22 MRPS24 MRPL37 GFM1:GDPMRPL48 MRPS16 MRPS21 MRPL24 MRPL13 MRPL27 MRPL53 MRPS21 Mitochondrial 16SrRNA CHCHD1 MRPL52 MRPL47 MRPS23 TUFM:GTP:aminoacyl-tRNAMRPL32 MRPL45 MRPS5 MRPL49 MRPL51 MRPL48 MRPS22 Mitochondrial 16SrRNA tRNAMRPL34 PTCD3 MRPS35 MRPL32 MRPL34 MRPL16 MRPS25 MRPS27 MRPS18B MRPS17 MRPS23 MRPL41 CHCHD1 MRPL18 MRPS33 MRPL13 MRPL32 MRPS22 MRPL32 mRNAMRPS27 MRPS28 MRPL10 MRPS7 MRPS16 PiMRPL49 MRPS14 MRPL3 MRPS17 MRPS12 MRPL43 55Sribosome:MRRF:GFM2:GTPAURKAIP1 MRPL45 MRPS30 MRPL35 MRPS22 MRPS17 MRPS36 MRPL9 MRPL52 MRPS28 MRPS18A MRPS22 TUFM Mitochondrial 16SrRNA MRPS28 MRPS12 MRPS35 Mitochondrial 16SrRNA MRPL9 GTP MRPS28 MRPS7 MRPL45 MRPL12 MRPL35 MRPL11 MRPS24 MRPL36 MRPL15 MRPS10 MRPL23 MRPL23 MRPL23 MRPL52 MRPS35 MRPL37 MRPL37 MRPL43 MRPL46 MRPS7 MRPL54 MRPL17 PTCD3 MRPL20 MRPL48 MRPL35 MRPL51 MRPS7 MRPS31 MRPL13 MRPL50 MRPL3 MRPL10 GADD45GIP1 MRPL3 MRPS33 MRPL55 MRPL49 MRPL11 MRPL23 MRPS25 MRPL10 MRPS24 MRPL54 GDPMRPS26 MRPS25 MRPL41 MRPL52 MRPS34 MRPL22 MRPL1 MRPL52 MRPS23 MRPL9 MRPS18C GFM1 MRPL27 MRPL19 MRPL43 MRPL30 MRPL37 MTIF2 fMet-tRNA(fMet)Mitochondrial 16SrRNA PTCD3 MRPS18C Mitochondrial 12SrRNA PTCD3 MRPL44 MRPL54 MRPS35 MRPL55 MRPL18 MRPL32 MRPS17 MRPL45 39S ribosomalsubunitMRPL32 MRPL4 MRPL21 MRPS23 MRPS21 MRPL33 MRPL1 MRPS22 MRPL40 MRPL48 MRPL55 MRPS33 MRPS34 PTCD3 MRPL42 MRPS15 GTP MTIF3MRPL14 DAP3 MRPS6 MRPL21 MRPL22 Mitochondrial 16SrRNA MRPL43 MRPS24 GADD45GIP1 MRPL34 MRPS33 MRPL14 MRPL18 PTCD3 MRPS36 MRPS5 MRPS35 MRPS21 MRPL4 MRPL38 GFM1:GTPTUFM:GDPICT1 MRPL52 MRPL32 MRPL44 MRPL11 MRPS36 MRPS35 DAP3 GADD45GIP1 MRPL54 MRPL41 MRPL1 MRPS6 MRRFMRPL47 MRPL30 MRPL42 MRPL24 Met-tRNA(Met)MRPS36 MRPS16 55Sribosome:mRNA:tRNA:peptidyl-tRNA at A-siteMRPL35 MRPL35 MRPS17 MRPL15 MRPS10 MRPL21 MRPS18B ICT1 MRPL38 MRPL9 MRPS28 MRPL2 MRPS28 MRPL52 MRPS17 MRPL49 MRPL52 MRPL12 MRPL33 MRPL1 MRPL50 MRPL18 MRPL43 MRPL19 MRPS12 MRPS18A MRPL54 MRPL22 GTP MRPL45 MRPL30 MRPS16 MRPL20 MRPL27 MRPS24 MRPS18A MRPS16 55Sribosome:mRNA:tRNAMRPL36 MRPS22 MRPS26 MRPS33 MRPL12 ICT1 MRPL28 MRPS28 55Sribosome:mRNA:fMet-tRNA:aminoacyl-tRNA:TUFM:GTPMRPS25 MTIF3 MRPS27 MRPL42 MRPS5 GDP MRPL44 GTP MRPL39 MRPL51 MRPL42 CHCHD1 MRPL27 MRPL12 MRPS14 AURKAIP1 MRPL20 MRPS24 MRPL19 MRPS18B MRPS14 CHCHD1 MRPS25 MRPL11 MRPS14 MRPL51 MTRF1L, ICT1MRPS12 MRPL45 MRPS36 MRPS34 MRPL51 MRPL44 MRPS35 MRPL4 MRPS21 55Sribosome:mRNA:fMet-tRNA:aminoacyl-tRNAMRPL38 GFM2:GTPMRPL28 MRPS35 MRPS10 MRPL43 MRPL43 MRPS15 MRPS34 MRPS10 MRPL1 MRPS27 MRPL20 MRPS18C MRPS25 MRPL46 MRPL46 MRPL54 MRPL14 MRPS30 MRPS34 GFM1 MRPS15 MRPS5 MRPL40 MRPS10 MRPS31 Mitochondrial 12SrRNA MRPS9 MRPL12 MRPL39 MRPS18A MRPS22 AURKAIP1 MRPL43 MRPL20 MRPS33 MRPL33 MRPL12 MRPS9 MRPS27 MRPS18B DAP3 MRPS23 MRPL17 MRPS10 MRPL53 MRPL2 MRPL28 MRPS28 MRPL39 MRPL14 GFM2:GDPMRPL40 MRPL37 MRPS21 MRPS5 MRPL42 MRPS7 Mitochondrial 12SrRNA MRPS18A MRPS30 MRPL30 MRPS15 MRPL41 MRPL24 MRPS25 MRPS18B MRPL44 MRPL43 MRPS15 PTCD3 MRPS23 MRPS11 MRPL14 MRPL28 MRPL3 MRPL45 MRPL53 DAP3 DAP3 MRPS27 MRPS7 Mitochondrial 12SrRNA 55Sribosome:mRNA:peptidyl-tRNA:MTRF1L:GTPMRPL37 MRPL48 GFM2 MRPL28 MRPS27 MRPS33 MRPL27 MRPS24 GDP MRPL11 MRPS35 MRPS11 MRPS31 MRPS9 MRPS23 MRPS10 MRPS18B GADD45GIP1 MRPL23 DAP3 MRPS6 GTP MRPS5 TUFM MRPS6 MRPL49 MRPL19 MRPL45 MRPS28 MRPL22 MRPL38 MRPS16 MRPS11 MRPS36 MRPL55 MRPL19 MRPL34 CHCHD1 MRPS33 MRPS25 AURKAIP1 MRPL20 MRPL45 MRPL1 MRPL36 MRPL24 MRPS6 MRPL17 MRPL38 55Sribosome:mRNA:tRNA:MRRFMRPS28 ICT1 MRPL30 CHCHD1 MRPL12 MRPL23 MRPL42 MRPL14 MRRF MRPL39 MRPS12 MRPS31 MRPS12 MRPS17 MRPL24 Mitochondrial 16SrRNA MRPS17 MRPL23 MRPS18B MRPL21 MRPS34 MRPS7 MRPS14 Mitochondrial 12SrRNA MRPL11 DAP3 MRPL46 MRPS9 MRPL54 THFMRPS36 MRPS9 MRPL33 GTP MRPS9 MRPS30 MRPL48 MRPS5 MRPL41 MRPS33 GDP MRPL22 MRPL55 MRPS31 MRPS18A MRPL23 MRPS36 MRPL2 ICT1 MRPL13 MRPL9 TUFM:TSFMMRPL17 MRPS6 MRPS23 MRPL16 MRPL44 MRPL51 MRPL42 MRPL51 MRPS11 MRPS14 MRPL16 MRPS23 MRPL17 MRPS18C MRPL47 MRPL13 MRPS12 MRPL14 PTCD3 MRPL16 MRPL53 MRPS23 MRPS21 MRPL15 MRPL14 MRPS5 MRPL19 MRPL16 MRPL35 MRPL4 MRPS24 AURKAIP1 MRPL54 MRPL30 MRPL53 MRPL46 MRPS9 MRPL42 MRPL47 MRPL2 MRPL54 MTIF2 MRPL40 MRPL33 MRPL18 MRPS30 MRPL40 GADD45GIP1 MRPL49 MRPS30 MRPS14 MRPL41 MRPS33 MRPS27 MRPL21 ICT1 MRPL15 MRPL33 MRPL48 MRPS36 MRPS21 MRPL48 MRPL34 MRPS35 MRPL14 polypeptideMRPS26 MRPS33 MRPL17 MRPS23 MRPS15 MRPL3 PTCD3 MRPL37 MRPL45 MRPS11 MRPL18 MRPL3 GADD45GIP1 MRPL14 MRPS7 MRPL19 MRPL47 MRPL18 MRPS26 MRPS18B MRPS11 4, 6, 159, 269, 28


Description

Of the roughly 1000 human mitochondrial proteins only 13 proteins, all of them hydrophobic inner membrane proteins that are components of the oxidative phosphorylation apparatus, are encoded in the mitochondrial genome and translated by mitoribosomes at the matrix face of the inner membrane (reviewed in Herrmann et al. 2012, Hallberg and Larsson 2014, Lightowlers et al. 2014). The remainder, including all proteins of the mitochondrial translation system, are encoded in the nucleus and imported from the cytosol into the mitochondrion. Translation in the mitochondrion reflects both the bacterial origin of the organelle and subsequent divergent evolution during symbiosis (reviewed in Huot et al. 2014, Richman et al. 2014). Human mitochondrial ribosomes have a low sedimentation coefficient of only 55S, but at 2.71 MDa they retain a similar mass to E. coli 70S particles. The 55S particles are protein-rich compared to both cytosolic ribosomes and eubacterial ribosomes. This is due to shorter mt-rRNAs, mitochondria-specific proteins, and numerous rearrangements in individual protein positions within the two ribosome subunits (inferred from bovine ribosomes in Sharma et al. 2003, Greber et al. 2014, Kaushal et al. 2014, reviewed in Agrawal and Sharma 2012).
Mitochondrial mRNAs have either no untranslated leader or short leaders of 1-3 nucleotides, with the exception of the 2 bicistronic transcripts, RNA7 and RNA14, which have overlapping orfs that encode ND4L/ND4 and ATP8/ATP6 respectively. Translation is believed to initiate with the mRNA binding the 28S subunit:MTIF3 (28S subunit:IF-3Mt, 28S subunit:IF2mt) complex together with MTIF2:GTP (IF-2Mt:GTP, IF2mt:GTP) at the matrix face of the inner membrane (reviewed in Christian and Spremulli 2012). MTIF3 can dissociate 55S particles in preparation for initiation, enhances formation of initiation complexes, and inhibits N-formylmethionine-tRNA (fMet-tRNA) binding to 28S subunits in the absence of mRNA. Binding of fMet-tRNA to the start codon of the mRNA results in a stable complex while absence of a start codon at the 5' end of the mRNA causes eventual dissociation of the mRNA from the 28S subunit. After recognition of a start codon, the 39S subunit then binds the stable complex, GTP is hydrolyzed, and the initiation factors MTIF3 and MTIF2:GDP dissociate.
Translation elongation then proceeds by cycles of aminoacyl-tRNAs binding, peptide bond formation, and displacement of deacylated tRNAs. In each cycle an aminoacyl-tRNA in a complex with TUFM:GTP (EF-Tu:GTP) binds at the A-site of the ribosome, GTP is hydrolyzed, and TUFM:GDP dissociates. The elongating polypeptide bonded to the tRNA at the P-site is transferred to the aminoacyl group at the A-site by peptide bond formation at the peptidyl transferase center, leaving a deacylated tRNA at the P-site and the elongating polypeptide attached to the tRNA at the A-site. The polypeptide is co-translationally inserted into the inner mitochondrial membrane via an interaction with OXA1L (Haque et al. 2010, reviewed in Ott and Hermann 2010). After peptide bond formation, GFM1:GTP (EF-Gmt:GTP) then binds the ribosome complex, GTP is hydrolyzed, GFM1:GDP dissociates, and the ribosome translocates 3 nucleotides in the 3' direction along the mRNA, relocating the polypeptide-tRNA to the P-site and allowing another cycle to begin. TUFM:GDP is regenerated to TUFM:GTP by the guanine nucleotide exchange factor TSFM (EF-Ts, EF-TsMt).
Translation is terminated when MTRF1L:GTP (MTRF1a:GTP) recognizes an UAA or UAG termination codon at the A-site of the ribosome (Tsuboi et al. 2009). GTP hydrolysis does not appear to be required. The tRNA-aminoacyl bond between the translated polypeptide and the final tRNA at the P-site is hydrolyzed by the 39S subunit, facilitating release of the polypeptide. MRRF (RRF) and GFM2:GTP (EF-G2mt:GTP) then act to release the remaining tRNA and mRNA from the ribosome and dissociate the 55S ribosome into 28S and 39S subunits.
Mutations have been identified in genes encoding mitochondrial ribosomal proteins and translation factors. These have been shown to be pathogenic, causing neurological and other diseases (reviewed in Koopman et al. 2013, Pearce et al. 2013). Source:Reactome.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114740view16:22, 25 January 2021ReactomeTeamReactome version 75
113184view11:25, 2 November 2020ReactomeTeamReactome version 74
112412view15:35, 9 October 2020ReactomeTeamReactome version 73
101316view11:20, 1 November 2018ReactomeTeamreactome version 66
100853view20:52, 31 October 2018ReactomeTeamreactome version 65
100394view19:26, 31 October 2018ReactomeTeamreactome version 64
99942view16:11, 31 October 2018ReactomeTeamreactome version 63
99498view14:44, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99147view12:41, 31 October 2018ReactomeTeamreactome version 62
93746view13:33, 16 August 2017ReactomeTeamreactome version 61
93261view11:18, 9 August 2017ReactomeTeamreactome version 61
87964view13:13, 25 July 2016RyanmillerOntology Term : 'translation pathway' added !
87963view13:13, 25 July 2016RyanmillerOntology Term : 'regulatory pathway' added !
86341view09:15, 11 July 2016ReactomeTeamreactome version 56
83252view10:32, 18 November 2015ReactomeTeamVersion54
81361view12:53, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
10-formyl-THFMetaboliteCHEBI:15637 (ChEBI)
28S

ribosomal

subunit:MTIF3:MTIF2:GTP:mRNA:fMet-tRNA		ComplexR-HSA-5368280 (Reactome)
28S ribosomal subunit:MTIF3ComplexR-HSA-5368269 (Reactome)
28S ribosomal subunitComplexR-HSA-5368239 (Reactome)
39S ribosomal subunitComplexR-HSA-5368233 (Reactome)
55S ribosome:MRRF:GFM2:GTPComplexR-HSA-5419282 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNA:TUFM:GTPComplexR-HSA-5389851 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNAComplexR-HSA-5389838 (Reactome)
55S ribosome:mRNA:fMet-tRNAComplexR-HSA-5368273 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA at P-siteComplexR-HSA-5419272 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA:MTRF1L:GTPComplexR-HSA-5419280 (Reactome)
55S ribosome:mRNA:tRNA:MRRFComplexR-HSA-5419275 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA at A-siteComplexR-HSA-5389843 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA:GFM1:GTPComplexR-HSA-5419267 (Reactome)
55S ribosome:mRNA:tRNAComplexR-HSA-5419262 (Reactome)
AURKAIP1 ProteinQ9NWT8 (Uniprot-TrEMBL)
CHCHD1 ProteinQ96BP2 (Uniprot-TrEMBL)
DAP3 ProteinP51398 (Uniprot-TrEMBL)
GADD45GIP1 ProteinQ8TAE8 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GFM1 ProteinQ96RP9 (Uniprot-TrEMBL)
GFM1:GDPComplexR-HSA-5419260 (Reactome)
GFM1:GTPComplexR-HSA-5419274 (Reactome)
GFM2 ProteinQ969S9 (Uniprot-TrEMBL)
GFM2:GDPComplexR-HSA-5419266 (Reactome)
GFM2:GTPComplexR-HSA-5419270 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
ICT1 ProteinQ14197 (Uniprot-TrEMBL)
MRPL1 ProteinQ9BYD6 (Uniprot-TrEMBL)
MRPL10 ProteinQ7Z7H8 (Uniprot-TrEMBL)
MRPL11 ProteinQ9Y3B7 (Uniprot-TrEMBL)
MRPL12 ProteinP52815 (Uniprot-TrEMBL)
MRPL13 ProteinQ9BYD1 (Uniprot-TrEMBL)
MRPL14 ProteinQ6P1L8 (Uniprot-TrEMBL)
MRPL15 ProteinQ9P015 (Uniprot-TrEMBL)
MRPL16 ProteinQ9NX20 (Uniprot-TrEMBL)
MRPL17 ProteinQ9NRX2 (Uniprot-TrEMBL)
MRPL18 ProteinQ9H0U6 (Uniprot-TrEMBL)
MRPL19 ProteinP49406 (Uniprot-TrEMBL)
MRPL2 ProteinQ5T653 (Uniprot-TrEMBL)
MRPL20 ProteinQ9BYC9 (Uniprot-TrEMBL)
MRPL21 ProteinQ7Z2W9 (Uniprot-TrEMBL)
MRPL22 ProteinQ9NWU5 (Uniprot-TrEMBL)
MRPL23 ProteinQ16540 (Uniprot-TrEMBL)
MRPL24 ProteinQ96A35 (Uniprot-TrEMBL)
MRPL27 ProteinQ9P0M9 (Uniprot-TrEMBL)
MRPL28 ProteinQ13084 (Uniprot-TrEMBL)
MRPL3 ProteinP09001 (Uniprot-TrEMBL)
MRPL30 ProteinQ8TCC3 (Uniprot-TrEMBL)
MRPL32 ProteinQ9BYC8 (Uniprot-TrEMBL)
MRPL33 ProteinO75394 (Uniprot-TrEMBL)
MRPL34 ProteinQ9BQ48 (Uniprot-TrEMBL)
MRPL35 ProteinQ9NZE8 (Uniprot-TrEMBL)
MRPL36 ProteinQ9P0J6 (Uniprot-TrEMBL)
MRPL37 ProteinQ9BZE1 (Uniprot-TrEMBL)
MRPL38 ProteinQ96DV4 (Uniprot-TrEMBL)
MRPL39 ProteinQ9NYK5 (Uniprot-TrEMBL)
MRPL4 ProteinQ9BYD3 (Uniprot-TrEMBL)
MRPL40 ProteinQ9NQ50 (Uniprot-TrEMBL)
MRPL41 ProteinQ8IXM3 (Uniprot-TrEMBL)
MRPL42 ProteinQ9Y6G3 (Uniprot-TrEMBL)
MRPL43 ProteinQ8N983 (Uniprot-TrEMBL)
MRPL44 ProteinQ9H9J2 (Uniprot-TrEMBL)
MRPL45 ProteinQ9BRJ2 (Uniprot-TrEMBL)
MRPL46 ProteinQ9H2W6 (Uniprot-TrEMBL)
MRPL47 ProteinQ9HD33 (Uniprot-TrEMBL)
MRPL48 ProteinQ96GC5 (Uniprot-TrEMBL)
MRPL49 ProteinQ13405 (Uniprot-TrEMBL)
MRPL50 ProteinQ8N5N7 (Uniprot-TrEMBL)
MRPL51 ProteinQ4U2R6 (Uniprot-TrEMBL)
MRPL52 ProteinQ86TS9 (Uniprot-TrEMBL)
MRPL53 ProteinQ96EL3 (Uniprot-TrEMBL)
MRPL54 ProteinQ6P161 (Uniprot-TrEMBL)
MRPL55 ProteinQ7Z7F7 (Uniprot-TrEMBL)
MRPL9 ProteinQ9BYD2 (Uniprot-TrEMBL)
MRPS10 ProteinP82664 (Uniprot-TrEMBL)
MRPS11 ProteinP82912 (Uniprot-TrEMBL)
MRPS12 ProteinO15235 (Uniprot-TrEMBL)
MRPS14 ProteinO60783 (Uniprot-TrEMBL)
MRPS15 ProteinP82914 (Uniprot-TrEMBL)
MRPS16 ProteinQ9Y3D3 (Uniprot-TrEMBL)
MRPS17 ProteinQ9Y2R5 (Uniprot-TrEMBL)
MRPS18A ProteinQ9NVS2 (Uniprot-TrEMBL)
MRPS18B ProteinQ9Y676 (Uniprot-TrEMBL)
MRPS18C ProteinQ9Y3D5 (Uniprot-TrEMBL)
MRPS21 ProteinP82921 (Uniprot-TrEMBL)
MRPS22 ProteinP82650 (Uniprot-TrEMBL)
MRPS23 ProteinQ9Y3D9 (Uniprot-TrEMBL)
MRPS24 ProteinQ96EL2 (Uniprot-TrEMBL)
MRPS25 ProteinP82663 (Uniprot-TrEMBL)
MRPS26 ProteinQ9BYN8 (Uniprot-TrEMBL)
MRPS27 ProteinQ92552 (Uniprot-TrEMBL)
MRPS28 ProteinQ9Y2Q9 (Uniprot-TrEMBL)
MRPS30 ProteinQ9NP92 (Uniprot-TrEMBL)
MRPS31 ProteinQ92665 (Uniprot-TrEMBL)
MRPS33 ProteinQ9Y291 (Uniprot-TrEMBL)
MRPS34 ProteinP82930 (Uniprot-TrEMBL)
MRPS35 ProteinP82673 (Uniprot-TrEMBL)
MRPS36 ProteinP82909 (Uniprot-TrEMBL)
MRPS5 ProteinP82675 (Uniprot-TrEMBL)
MRPS6 ProteinP82932 (Uniprot-TrEMBL)
MRPS7 ProteinQ9Y2R9 (Uniprot-TrEMBL)
MRPS9 ProteinP82933 (Uniprot-TrEMBL)
MRRF ProteinQ96E11 (Uniprot-TrEMBL)
MRRFProteinQ96E11 (Uniprot-TrEMBL)
MTFMTProteinQ96DP5 (Uniprot-TrEMBL)
MTIF2 ProteinP46199 (Uniprot-TrEMBL)
MTIF2:GTPComplexR-HSA-5368285 (Reactome)
MTIF2ProteinP46199 (Uniprot-TrEMBL)
MTIF3 ProteinQ9H2K0 (Uniprot-TrEMBL)
MTIF3ProteinQ9H2K0 (Uniprot-TrEMBL)
MTRF1L ProteinQ9UGC7 (Uniprot-TrEMBL)
MTRF1L, ICT1R-HSA-5432633 (Reactome) Both MTRF1L and ICT1 can bind a standard stop codon in the A-site of the ribosome and cause release of the polypeptide. ICT1 can also cause release of ribosomes stalled in non-standard conformations (e.g. non-standard stop codons, mRNA lacking a stop codon) (inferred from pig mitoribosomes in Akabane et al. 2014).
Met-tRNA(Met)MetaboliteR-HSA-379780 (Reactome)
Mitochondrial 12S rRNA ProteinENST00000389680 (ENSEMBL)
Mitochondrial 16S rRNA ProteinENST00000387347 (ENSEMBL)
PTCD3 ProteinQ96EY7 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
THFMetaboliteCHEBI:15635 (ChEBI)
TSFM ProteinP43897 (Uniprot-TrEMBL)
TSFMProteinP43897 (Uniprot-TrEMBL)
TUFM ProteinP49411 (Uniprot-TrEMBL)
TUFM:GDPComplexR-HSA-5389856 (Reactome)
TUFM:GTP:aminoacyl-tRNAComplexR-HSA-5389855 (Reactome)
TUFM:GTPComplexR-HSA-5389853 (Reactome)
TUFM:TSFMComplexR-HSA-5419263 (Reactome)
aminoacyl-tRNAR-HSA-5389847 (Reactome)
fMet-tRNA(fMet)R-HSA-5368270 (Reactome)
mRNAR-NUL-5368267 (Reactome) Mitochondrial mRNAs are characterized by lacking or having very short (1-3 nucleotide) untranslated leaders and no introns. The mitochondrial genome of humans encodes only 13 polypeptides.
polypeptideR-NUL-5419287 (Reactome)
tRNA(Met)MetaboliteR-HSA-379741 (Reactome)
tRNAR-HSA-5389844 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
10-formyl-THFR-HSA-5389841 (Reactome)
28S

ribosomal

subunit:MTIF3:MTIF2:GTP:mRNA:fMet-tRNA		ArrowR-HSA-5389849 (Reactome)
28S

ribosomal

subunit:MTIF3:MTIF2:GTP:mRNA:fMet-tRNA		R-HSA-5389839 (Reactome)
28S

ribosomal

subunit:MTIF3:MTIF2:GTP:mRNA:fMet-tRNA		mim-catalysisR-HSA-5389839 (Reactome)
28S ribosomal subunit:MTIF3ArrowR-HSA-5368279 (Reactome)
28S ribosomal subunit:MTIF3R-HSA-5389849 (Reactome)
28S ribosomal subunitArrowR-HSA-5419273 (Reactome)
28S ribosomal subunitR-HSA-5368279 (Reactome)
39S ribosomal subunitArrowR-HSA-5419273 (Reactome)
39S ribosomal subunitR-HSA-5389839 (Reactome)
55S ribosome:MRRF:GFM2:GTPArrowR-HSA-5419277 (Reactome)
55S ribosome:MRRF:GFM2:GTPR-HSA-5419273 (Reactome)
55S ribosome:MRRF:GFM2:GTPmim-catalysisR-HSA-5419273 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNA:TUFM:GTPArrowR-HSA-5389848 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNA:TUFM:GTPR-HSA-5389842 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNA:TUFM:GTPmim-catalysisR-HSA-5389842 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNAArrowR-HSA-5389842 (Reactome)
55S ribosome:mRNA:fMet-tRNA:aminoacyl-tRNAR-HSA-5389857 (Reactome)
55S ribosome:mRNA:fMet-tRNAArrowR-HSA-5389839 (Reactome)
55S ribosome:mRNA:fMet-tRNAR-HSA-5389848 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA at P-siteArrowR-HSA-5419279 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA at P-siteR-HSA-5419264 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA:MTRF1L:GTPArrowR-HSA-5419264 (Reactome)
55S ribosome:mRNA:peptidyl-tRNA:MTRF1L:GTPR-HSA-5419271 (Reactome)
55S ribosome:mRNA:tRNA:MRRFArrowR-HSA-5419281 (Reactome)
55S ribosome:mRNA:tRNA:MRRFR-HSA-5419277 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA at A-siteArrowR-HSA-5389857 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA at A-siteR-HSA-5419261 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA:GFM1:GTPArrowR-HSA-5419261 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA:GFM1:GTPR-HSA-5419279 (Reactome)
55S ribosome:mRNA:tRNA:peptidyl-tRNA:GFM1:GTPmim-catalysisR-HSA-5419279 (Reactome)
55S ribosome:mRNA:tRNAArrowR-HSA-5419271 (Reactome)
55S ribosome:mRNA:tRNAR-HSA-5419281 (Reactome)
GDPArrowR-HSA-5389839 (Reactome)
GDPArrowR-HSA-5419269 (Reactome)
GDPArrowR-HSA-5419271 (Reactome)
GFM1:GDPArrowR-HSA-5419279 (Reactome)
GFM1:GTPR-HSA-5419261 (Reactome)
GFM2:GDPArrowR-HSA-5419273 (Reactome)
GFM2:GTPR-HSA-5419277 (Reactome)
GTPR-HSA-5419264 (Reactome)
GTPR-HSA-5419268 (Reactome)
MRRFArrowR-HSA-5419273 (Reactome)
MRRFR-HSA-5419281 (Reactome)
MTFMTmim-catalysisR-HSA-5389841 (Reactome)
MTIF2:GTPR-HSA-5389849 (Reactome)
MTIF2ArrowR-HSA-5389839 (Reactome)
MTIF3ArrowR-HSA-5389839 (Reactome)
MTIF3R-HSA-5368279 (Reactome)
MTRF1L, ICT1ArrowR-HSA-5419271 (Reactome)
MTRF1L, ICT1R-HSA-5419264 (Reactome)
Met-tRNA(Met)R-HSA-5389841 (Reactome)
PiArrowR-HSA-5389839 (Reactome)
PiArrowR-HSA-5389842 (Reactome)
PiArrowR-HSA-5419271 (Reactome)
PiArrowR-HSA-5419273 (Reactome)
PiArrowR-HSA-5419279 (Reactome)
R-HSA-5368279 (Reactome) As inferred from bovine mitochondrial homologs, MTIF3 (IF-3Mt, IF3mt) binds the 28S ribosomal subunit in preparation for binding mRNA and initiating translation. MTIF3 also dissociates 55S particles that have not already been dissociated by GFM2 plus MRRF and displaces N-formylmethionyl-tRNA from the 28S subunit in the absence of mRNA but cannot displace mRNA from the 28S subunit. The activity of MTIF3 is necessary for translation initiation.. The 28S subunit associates with the matrix-side face of the inner mitochondrial membrane and translation products are inserted directly into the membrane.
R-HSA-5389839 (Reactome) As inferred from bovine homologs, the 39S ribosomal subunit binds the 28S subunit:mRNA:N-formylmethionyl-tRNA complex, MTIF2 hydrolyzes GTP, then MTIF2, GDP, and MTIF3 dissociate. (MTIF2 has a very low affinity for GDP so it is unclear whether MTIF2 and GDP remain associated after hydrolysis of GTP.) The 28S subunit, 39S subunit, and 55S holoribosome associate with the inner mitochondrial membrane during translation and in the absence of translation.
R-HSA-5389841 (Reactome) Like bacteria, mitochondria initiate translation with N-formylmethionine. Unlike bacteria, mammalian mitochondria do not have a tRNA dedicated to N-formylmethionine. Instead, the mitochondrial enzyme MTFMT (methionyl-tRNA formyltransferase, FMT, FMT1) transfers a formyl group from 10-formyltetrahydrofolate (10-formyl-THF) to the amino group of methionyl-tRNA in a portion of the methionyl-tRNAs in the matrix.
R-HSA-5389842 (Reactome) As inferred from bovine homologs, interaction of the cognate aminoacyl-tRNA in the A-site with the codon in the mRNA causes TUFM (EF-Tu) to hydrolyze GTP. TUFM:GDP then dissociates from the ribosome.
R-HSA-5389845 (Reactome) As inferred from bovine homologs, TUFM:GTP (EF-Tu:GTP) binds an aminoacyl-tRNA to form the ternary complex.
R-HSA-5389848 (Reactome) As inferred from bovine homologs, the ternary complex containing TUFM:GTP (EF-Tu:GTP) and aminoacyl-tRNA enters the A-site of the 55S ribosome (reviewed in Christian and Spremulli 2012).
R-HSA-5389849 (Reactome) As inferred from bovine homologs, the 28S ribosomal subunit in a complex with MTIF3 (IF-3Mt, IF3mt) binds mRNA and, at some point, MTIF2:GTP (IF-2Mt:GTP, IF2mt:GTP). If an initiation codon is present at the 5' end of the mRNA then MTIF2:GTP assists the binding of N-formylmethionyl-tRNA and a stable, productive initiation complex results. If no initiation codon is present, the mRNA slides through the 28S subunit and then dissociates.
R-HSA-5389857 (Reactome) As inferred from bovine homologs, the ribosome catalyzes formation of a peptide bond between the aminoacyl group of the aminoacyl-tRNA at the A-site and the peptidyl-tRNA at the P-site. The result is a polypeptide, longer by one amino acid, attached to the tRNA at the A-site by an ester bond. A deacylated tRNA remains at the P-site. 55S ribosomes associate with the inner mitochondrial membrane and the translation products are cotranslationally inserted into the inner membrane.
R-HSA-5419261 (Reactome) GFMT1:GTP (EF-G1mt:GTP) binds ribosomes possessing a peptidyl-tRNA at the A site and an empty P site (Bhargava et al. 2004, Tsuboi et al. 2009, inferred from bovine homologs in Chung and Spremulli 1990).
R-HSA-5419264 (Reactome) MTRF1L (mtRF1a) binds the stop codons UAA and UAG of the mRNA when they are in the A site of the ribosome (Soleimanpour-Lichaei 2007, Nozaki et al. 2008). (The UGA codon is recognized by the tryptophan tRNA in mitochondrial translation.) ICT1 can also bind standard stop codons in the A-site (inferred from pig mitochondrial ribosomes in Akabane et al. 2014). MTRF1 was also thought to play a role in translation termination by recognizing the unconventional termination codons AGA and AGG (Zhang and Spremulli 1998, Young et al. 2010) but frameshifting is now confirmed in the termination mechanism of these codons (Temperley et al. 2010). Structural features of MTRF1 have been reported suggesting it could recognize an empty A-site (Huynen et al. 2012) or UAA and UAG codons (Lind et al. 2013) however there is no direct experimental data to confirm these last two postulates.
R-HSA-5419268 (Reactome) As inferred from bovine homologs, TSFM (EF-Ts, EF-TsMt) acts as a guanine nucleotide exchange factor for TUFM (EF-Tu). In the second step of the process TUFM in the TUFM:TSFM complex binds GTP and TSFM is released, yielding TUFM:GTP and TSFM.
R-HSA-5419269 (Reactome) As inferred from bovine homologs, TSFM (EF-Ts, EF-TsMt) acts as a guanine nucleotide exchange factor to regenerate TUFM:GTP (EF-Tu:GTP) from TUFM:GDP. In the first step of the process TSFM binds TUFM:GDP and displaces GDP, yielding a TSFM:TUFM complex and GDP.
R-HSA-5419271 (Reactome) Binding of the MTRF1L (MTRF1a) termination factor triggers hydrolysis of the peptidyl-tRNA bond by the 39S subunit of the ribosome and release of the translated polypeptide (Soleimanpour-Lichaei et al. 2007, Nozaki et al. 2008, reviewed in Christian and Spremulli 2012). MTRF1L hydrolyzes GTP during the reaction. Stalled ribosomes are rescued by binding of an ICT1 protein in addition to the ICT1 subunit integrated in the 39S subunit (Richter et al. 2010, Akabane et al. 2014).
R-HSA-5419273 (Reactome) When complexed with ribosomes GFM2 (EF-G2mt) hydrolyzes GTP and, together with MRRF, acts as a ribosome releasing factor by splitting 55S ribosomes into 28S and 39S subunits (Tsuboi et al. 2009). Though GTP is hydrolyzed during the reaction, hydrolysis is not necessary for splitting the 55S ribosome into 39S and 28S subunits, but is necessary for dissociation of GFM2 (as GFM2:GDP) and MRRF from the large ribosomal subunit after splitting (Tsuboi et al. 2009).
R-HSA-5419277 (Reactome) GFM2:GTP (EF-G2mt:GTP) joins MRRF at the A site of the ribosome after translation has been terminated by MTRF1L (MTRF1a) at a stop codon.
R-HSA-5419279 (Reactome) GFM1 (EF-Gmt, EF-G1mt) of the GFM1:GTP complex hydrolyzes GTP, yielding GFM1:GDP (Tsuboi et al. 2009). The hydrolysis of GTP drives translocation of the peptidyl-tRNA from the A-site to the P-site with consequent ejection of the deacylated tRNA from the P-site and translocation of the ribosome in the 3' direction along the mRNA (Bhargava et al. 2004, Tsuboi et al. 2009, inferred from bovine homologs in Chung and Spremulli 1990).
R-HSA-5419281 (Reactome) The mitochondrial ribosome releasing factor MRRF (RRF) binds the 55S ribosome at the A-site after translation has been terminated by MTRF1L (MTRF1a) at a stop codon and the translated polypeptide has been hydrolyzed from the last tRNA, which remains in the P-site (Rorbach et al. 2008).
THFArrowR-HSA-5389841 (Reactome)
TSFMArrowR-HSA-5419268 (Reactome)
TSFMR-HSA-5419269 (Reactome)
TUFM:GDPArrowR-HSA-5389842 (Reactome)
TUFM:GDPR-HSA-5419269 (Reactome)
TUFM:GTP:aminoacyl-tRNAArrowR-HSA-5389845 (Reactome)
TUFM:GTP:aminoacyl-tRNAR-HSA-5389848 (Reactome)
TUFM:GTPArrowR-HSA-5419268 (Reactome)
TUFM:GTPR-HSA-5389845 (Reactome)
TUFM:TSFMArrowR-HSA-5419269 (Reactome)
TUFM:TSFMR-HSA-5419268 (Reactome)
aminoacyl-tRNAR-HSA-5389845 (Reactome)
fMet-tRNA(fMet)ArrowR-HSA-5389841 (Reactome)
fMet-tRNA(fMet)R-HSA-5389849 (Reactome)
mRNAArrowR-HSA-5419277 (Reactome)
mRNAR-HSA-5389849 (Reactome)
polypeptideArrowR-HSA-5419271 (Reactome)
tRNA(Met)ArrowR-HSA-5419279 (Reactome)
tRNAArrowR-HSA-5419277 (Reactome)
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