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Review

Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors

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Pages 117-131 | Received 10 Sep 2021, Accepted 02 Dec 2021, Published online: 20 Dec 2021

References

  • Roger AJ, Muñoz-Gómez SA, Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177–92.
  • Petrov AS, Wood EC, Bernier CR, et al. Structural patching fosters divergence of mitochondrial ribosomes. Mol Biol Evol. 2019;36(2):207–219.
  • Gustafsson CM, Falkenberg M, Larsson N-G. Maintenance and expression of mammalian mitochondrial DNA. Annu Rev Biochem. 2016;85(1):133–160.
  • Ferrari A, Del’Olio S, Barrientos A. The diseased mitoribosome. FEBS Lett. 2021;595(8):1025–1061.
  • Hock DH, Robinson DRL, Stroud DA. Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome. Biochem J. 2020;477(21):4085–4132.
  • Lopez Sanchez MIG, Krüger A, Shiriaev DI, et al. Human mitoribosome biogenesis and its emerging links to disease. IJMS. 2021;22(8):3827.
  • Rodnina MV, Wintermeyer W. Recent mechanistic insights into eukaryotic ribosomes. Curr Opin Cell Biol. 2009;21(3):435–443.
  • Kummer E, Ban N. Mechanisms and regulation of protein synthesis in mitochondria. Nat Rev Mol Cell Biol. 2021;22(5):307–325.
  • Temperley RJ, Wydro M, Lightowlers RN, et al. Human mitochondrial mRNAs—like members of all families, similar but different. Biochim Biophys Acta. 2010;1797(6–7):1081–1085.
  • Brown A, Amunts A, Bai XC, et al. Structure of the large ribosomal subunit from human mitochondria. Science. 2014;346(6210):718–722.
  • Greber BJ, Boehringer D, Leibundgut M, et al. The complete structure of the large subunit of the mammalian mitochondrial ribosome. Nature. 2014;515(7526):283–286.
  • Amunts A, Brown A, Toots J, et al. The structure of the human mitochondrial ribosome. Science. 2015;348(6230):95–98.
  • Greber BJ, Bieri P, Leibundgut M, et al. The complete structure of the 55S mammalian mitochondrial ribosome. Science. 2015;348(6232):303–308.
  • Müller C, Crowe-mcauliffe C, Wilson DN. Ribosome rescue pathways in bacteria. Front Microbiol. 2021;12:652980.
  • Aibara S, Singh V, Modelska A, et al. Structural basis of mitochondrial translation. eLife. 2020;9. DOI:10.7554/eLife.58362
  • Englmeier R, Pfeffer S, Förster F. Structure of the human mitochondrial ribosome studied in situ by cryoelectron tomography. Structure. 2017;25(10):1574–1581.e2.
  • Kummer E, Leibundgut M, Rackham O, et al. Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM. Nature. 2018;560(7717):263–267.
  • Itoh Y, Andréll J, Choi A, et al. Mechanism of membrane-tethered mitochondrial protein synthesis. Science. 2021;371(6531):846–849.
  • Desai N, Yang H, Chandrasekaran V, et al. Elongational stalling activates mitoribosome-associated quality control. Science. 2020;370(6520):1105–1110.
  • Greber BJ, Ban N. Structure and function of the mitochondrial ribosome. Annu Rev Biochem. 2016;85(1):103–132.
  • Sharma MR, Koc EC, Datta PP, et al. Structure of the mammalian mitochondrial ribosome reveals an expanded functional role for its component proteins. Cell. 2003;115(1):97–108.
  • Liu Q, Fredrick K. Intersubunit bridges of the bacterial ribosome. J Mol Biol. 2016;428(10):2146–2164.
  • Gaur R, Grasso D, Datta PP, et al. A single mammalian mitochondrial translation initiation factor functionally replaces two bacterial factors. Mol Cell. 2008;29(2):180–190.
  • Yassin AS, Haque ME, Datta PP, et al. Insertion domain within mammalian mitochondrial translation initiation factor 2 serves the role of eubacterial initiation factor 1. Proc Natl Acad Sci USA. 2011;108(10):3918–3923.
  • Christian BE, Spremulli LL. Evidence for an active role of IF3mt in the initiation of translation in mammalian mitochondria. Biochemistry. 2009;48(15):3269–3278.
  • Koripella RK, Sharma MR, Haque ME, et al. Structure of human mitochondrial translation initiation factor 3 bound to the small ribosomal subunit. iScience. 2019;12:76–86.
  • Khawaja A, Itoh Y, Remes C, et al. Distinct pre-initiation steps in human mitochondrial translation. Nat Commun. 2020;11(1). DOI:10.1038/s41467-020-16503-2
  • Lee M, Matsunaga N, Akabane S, et al. Reconstitution of mammalian mitochondrial translation system capable of correct initiation and long polypeptide synthesis from leaderless mRNA. Nucleic Acids Res. 2021;49(1):371–382.
  • Rodnina MV. Translation in Prokaryotes. Cold Spring Harb Perspect Biol. 2018;10(9):a032664.
  • Ayyub SA, Varshney U. Translation initiation in mammalian mitochondria- a prokaryotic perspective. RNA Biol. 2019;17(2):165–175.
  • Rudler DL, Hughes LA, Perks KL, et al. Fidelity of translation initiation is required for coordinated respiratory complex assembly. Sci Adv. 2019;5(12):eaay2118.
  • Yamamoto H, Wittek D, Gupta R, et al. 70S-scanning initiation is a novel and frequent initiation mode of ribosomal translation in bacteria. Proc Natl Acad Sci USA. 2016;113(9):E1180–9.
  • Goyal A, Belardinelli R, Rodnina MV. Non-canonical binding site for bacterial initiation factor 3 on the large ribosomal subunit. CellReports. 2017;20:3113–3122.
  • Kuzmenko A, Derbikova K, Salvatori R, et al. Aim-less translation: loss of Saccharomyces cerevisiae mitochondrial translation initiation factor mIF3/Aim23 leads to unbalanced protein synthesis. Sci Rep. 2016;6(1):1–9.
  • Chicherin IV, Baleva MV, Levitskii SA, et al. Initiation factor 3 is dispensable for mitochondrial translation in cultured human cells. Sci Rep. 2020;10(1):7110–7111.
  • Cruz-Zaragoza LD, Dennerlein S, Linden A, et al. An in vitro system to silence mitochondrial gene expression. Cell. 2021;184(23):5824–5837.e15.
  • Ott M, Amunts A, Brown A. Organization and regulation of mitochondrial protein synthesis. Annu Rev Biochem. 2016;85(1):77–101.
  • Woriax VL, Bullard JM, Ma L, et al. Mechanistic studies of the translational elongation cycle in mammalian mitochondria. Biochim Biophys Acta. 1997;1352(1):91–101.
  • Cai Y-C, Bullard JM, Thompson NL, et al. Interaction of mitochondrial elongation factor Tu with aminoacyl-tRNA and elongation factor Ts. J Biol Chem. 2000;275(27):20308–20314.
  • Voorhees RM, Schmeing TM, Kelley AC, et al. The mechanism for activation of GTP hydrolysis on the ribosome. Science. 2010;330(6005):835–838.
  • Schwartzbach CJ, Spremulli LL. Bovine mitochondrial protein synthesis elongation factors. Identification and initial characterization of an elongation factor Tu-elongation factor Ts complex. J Biol Chem. 1989;264(32):19125–19131.
  • Schwartzbach CJ, Spremulli LL. Interaction of animal mitochondrial EF-Tu.EF-Ts with aminoacyl-tRNA, guanine nucleotides, and ribosomes. J Biol Chem. 1991;266(25):16324–16330.
  • Rodnina MV, Peske F, Peng B-Z, et al. Converting GTP hydrolysis into motion: versatile translational elongation factor G. Biol Chem. 2019;401(1):131–142.
  • Tsuboi M, Morita H, Nozaki Y, et al. Takeuchi N. EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis. Mol Cell. 2009;35(4):502–510.
  • Koripella RK, Sharma MR, Risteff P, et al. Structural insights into unique features of the human mitochondrial ribosome recycling. Proc Natl Acad Sci USA. 2019;116(17):8283–8288.
  • Koripella RK, Deep A, Agrawal EK, et al. Distinct mechanisms of the human mitoribosome recycling and antibiotic resistance. Nat Commun. 2021;12(1). DOI:10.1038/s41467-021-23726-4
  • Kummer E, Schubert KN, Schoenhut T, et al. Structural basis of translation termination, rescue, and recycling in mammalian mitochondria. Mol Cell. 2021;81(12):2566–2582.e6.
  • Kummer E, Ban N. Structural insights into mammalian mitochondrial translation elongation catalyzed by mtEFG1. EMBO J. 2020;39(15):e104820.
  • Koripella RK, Sharma MR, Bhargava K, et al. Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of mitochondrial translation elongation. Nat Commun. 2020;11(1). DOI:10.1038/s41467-020-17715-2
  • Capecchi MR. Polypeptide chain termination in vitro: isolation of a release factor. Proc Natl Acad Sci USA. 1967;58(3):1144–1151.
  • Caskey CT, Tompkins R, Scolnick E, et al. Sequential translation of trinucleotide codons for the initiation and termination of protein synthesis. Science. 1968;162(3849):135–138.
  • Scolnick E, Tompkins R, Caskey T, et al. Release factors differing in specificity for terminator codons. Proc Natl Acad Sci USA. 1968;61(2):768–774.
  • Ito K, Uno M, Nakamura Y. A tripeptide “anticodon” deciphers stop codons in messenger RNA. Nature. 2000;403(6770):680–684.
  • Korostelev A, Asahara H, Lancaster L, et al. Crystal structure of a translation termination complex formed with release factor RF2. Proc Natl Acad Sci USA. 2008;105(50):19684–19689.
  • Laurberg M, Asahara H, Korostelev A, et al. Structural basis for translation termination on the 70S ribosome. Nature. 2008;454(7206):852–857.
  • Petry S, Brodersen DE, Murphy FV, et al. Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon. Cell. 2005;123(7):1255–1266.
  • Weixlbaumer A, Jin H, Neubauer C, et al. Insights into translational termination from the structure of RF2 bound to the ribosome. Science. 2008;322(5903):953–956.
  • Hetrick B, Lee K, Joseph S. Kinetics of stop codon recognition by release factor 1. Biochemistry. 2009;48(47):11178–11184.
  • Rawat UBS, Zavialov AV, Sengupta J, et al. A cryo-electron microscopic study of ribosome-bound termination factor RF2. Nature. 2003;421(6918):87–90.
  • Frolova LY, Tsivkovskii RY, Sivolobova GF, et al. Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis. RNA. 1999;5(8):1014–1020.
  • Mora L, Heurgué-Hamard V, Champ S, et al. The essential role of the invariant GGQ motif in the function and stability in vivo of bacterial release factors RF1 and RF2. Mol Microbiol. 2003;47(1):267–275.
  • Barrell BG, Bankier AT, Drouin J. A different genetic code in human mitochondria. Nature. 1979;282(5735):189–194.
  • Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290(5806):457–465.
  • Temperley R, Richter R, Dennerlein S, et al. Hungry codons promote frameshifting in human mitochondrial ribosomes. Science. 2010;327(5963):301.
  • Lee CC, Timms KM, Trotman CN, et al. Isolation of a rat mitochondrial release factor. Accommodation of the changed genetic code for termination. J Biol Chem. 1987;262(8):3548–3552.
  • Zhang Y, Spremulli LL. Identification and cloning of human mitochondrial translational release factor 1 and the ribosome recycling factor. Biochim Biophys Acta. 1998;1443(1–2):245–250.
  • Lind C, Sund J, Åqvist J. Codon-reading specificities of mitochondrial release factors and translation termination at non-standard stop codons. Nat Commun. 2013;4(1). DOI:10.1038/ncomms3940
  • Nozaki Y, Matsunaga N, Ishizawa T, et al. HMRF1L is a human mitochondrial translation release factor involved in the decoding of the termination codons UAA and UAG. Genes Cells. 2008;13(5):429–438.
  • Soleimanpour-Lichaei HR, Kühl I, Gaisne M, et al. mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG. Mol Cell. 2007;27(5):745–757.
  • Young DJ, Edgar CD, Murphy J, et al. Bioinformatic, structural, and functional analyses support release factor-like MTRF1 as a protein able to decode nonstandard stop codons beginning with adenine in vertebrate mitochondria. RNA. 2010;16(6):1146–1155.
  • Huynen MA, Duarte I, Chrzanowska-Lightowlers ZMA, et al. Structure based hypothesis of a mitochondrial ribosome rescue mechanism. Biol Direct. 2012;7(1):1–10.
  • Janosi L, Shimizu I, Kaji A. Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth. Proc Natl Acad Sci USA. 1994;91(10):4249–4253.
  • Rorbach J, Richter R, Wessels HJ, et al. The human mitochondrial ribosome recycling factor is essential for cell viability. Nucleic Acids Res. 2008;36(18):5787–5799.
  • Leipe DD, Wolf YI, Koonin EV, et al. Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol. 2002;317(1):41–72.
  • Lin J, Gagnon MG, Bulkley D, et al. Conformational changes of elongation factor G on the ribosome during tRNA translocation. Cell. 2015;160(1–2):219–227.
  • Iwakura N, Yokoyama T, Quaglia F, et al. Chemical and structural characterization of a model Post-Termination Complex (PoTC) for the ribosome recycling reaction: evidence for the release of the mRNA by RRF and EF-G. PLoS One. 2017;12(5):e0177972.
  • Weixlbaumer A, Petry S, Dunham CM, et al. Crystal structure of the ribosome recycling factor bound to the ribosome. Nat Struct Mol Biol. 2007;14(8):733–737.
  • Zhou D, Tanzawa T, Lin J, et al. Structural basis for ribosome recycling by RRF and tRNA. Nat Struct Mol Biol. 2020;27(1):25–32.
  • Gao N, Zavialov AV, Ehrenberg M, et al. Specific interaction between EF-G and RRF and its implication for GTP-dependent ribosome splitting into subunits. J Mol Biol. 2007;374(5):1345–1358.
  • Fu Z, Kaledhonkar S, Borg A, et al. Key intermediates in ribosome recycling visualized by time-resolved cryoelectron microscopy. Structure. 2016;24(12):2092–2101.
  • Samatova E, Daberger J, Liutkute M, et al. Translational control by ribosome pausing in bacteria: how a non-uniform pace of translation affects protein production and folding. Front Microbiol. 2020;11:619430.
  • Richter-Dennerlein R, Oeljeklaus S, Lorenzi I, et al. Mitochondrial protein synthesis adapts to influx of nuclear-encoded protein. Cell. 2016;167(2):471–483.e10.
  • Wang C, Richter-Dennerlein R, Pacheu-Grau D, et al. MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome-nascent chain complex. EMBO Rep. 2020;21(1):e48833.
  • Buskirk AR, Green R. Ribosome pausing, arrest and rescue in bacteria and eukaryotes. Philos Trans R Soc Lond B Biol Sci. 2017;372(1716):20160183.
  • Nürenberg-Goloub E, Tampé R. Ribosome recycling in mRNA translation, quality control, and homeostasis. Biol Chem. 2019;401(1):47–61.
  • Lytvynenko I, Paternoga H, Thrun A, et al. Alanine tails signal proteolysis in bacterial ribosome-associated quality control. Cell. 2019;178(1):76–90.e22.
  • Keiler KC. Mechanisms of ribosome rescue in bacteria. Nat Rev Microbiol. 2015;13(5):285–297.
  • Hudson BH, Zaher HS. Ribosomes left in the dust: diverse strategies for Peptide-mediated translation stalling. Mol Cell. 2014;56(3):345–346.
  • Karzai AW, Susskind MM, Sauer RT. SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA). EMBO J. 1999;18(7526):3793–3799.
  • Keiler KC, Waller PR, Sauer RT. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science. 1996;271(5251):990–993.
  • Neubauer C, Gillet R, Kelley AC, et al. Decoding in the absence of a codon by tmRNA and SmpB in the ribosome. Science. 2012;335(6074):1366–1369.
  • Ramrath DJF, Yamamoto H, Rother K, et al. The complex of tmRNA-SmpB and EF-G on translocating ribosomes. Nature. 2012;485(7399):526–529.
  • Yamamoto Y, Sunohara T, Jojima K, et al. SsrA-mediated trans -translation plays a role in mRNA quality control by facilitating degradation of truncated mRNAs. RNA. 2003;9(4):408–418.
  • Chadani Y, Ono K, Ozawa S-I, et al. Ribosome rescue by Escherichia coli ArfA (YhdL) in the absence of trans-translation system. Mol Microbiol. 2010;78(4):796–808.
  • Chadani Y, Ito K, Kutsukake K, et al. ArfA recruits release factor 2 to rescue stalled ribosomes by peptidyl-tRNA hydrolysis in Escherichia coli. Mol Microbiol. 2012;86(1):37–50.
  • Shimizu Y. ArfA recruits RF2 into stalled ribosomes. J Mol Biol. 2012;423(4):624–631.
  • Huter P, Müller C, Beckert B, et al. Structural basis for ArfA-RF2-mediated translation termination on mRNAs lacking stop codons. Nature. 2017;541(7638):546–549.
  • Zeng F, Chen Y, Remis J, et al. Structural basis of co-translational quality control by ArfA and RF2 bound to ribosome. Nature. 2017;541(7638):554–557.
  • Chadani Y, Matsumoto E, Aso H, et al. trans-translation-mediated tight regulation of the expression of the alternative ribosome-rescue factor ArfA in Escherichia coli. Genes Genet Syst. 2011;86(3):151–163.
  • Garza-Sánchez F, Schaub RE, Janssen BD, et al. tmRNA regulates synthesis of the ArfA ribosome rescue factor. Mol Microbiol. 2011;80(5):1204–1219.
  • Feaga HA, Viollier PH, Keiler KC. Release of nonstop ribosomes is essential. mBio. 2014;5(6):e01916.
  • Chadani Y, Ono K, Kutsukake K, et al. Escherichia coli YaeJ protein mediates a novel ribosome-rescue pathway distinct from SsrA- and ArfA-mediated pathways. Mol Microbiol. 2011;80(3):772–785.
  • Handa Y, Inaho N, Nameki N. YaeJ is a novel ribosome-associated protein in Escherichia coli that can hydrolyze peptidyl-tRNA on stalled ribosomes. Nucleic Acids Res. 2011;39(5):1739–1748.
  • Chan K-H, Petrychenko V, Mueller C, et al. Mechanism of ribosome rescue by alternative ribosome-rescue factor B. Nat Commun. 2020;11(1). DOI:10.1038/s41467-020-17853-7
  • Gagnon MG, Seetharaman SV, Bulkley D, et al. Structural basis for the rescue of stalled ribosomes: structure of YaeJ bound to the ribosome. Science. 2012;335(6074):1370–1372.
  • Kogure H, Handa Y, Nagata M, et al. Identification of residues required for stalled-ribosome rescue in the codon-independent release factor YaeJ. Nucleic Acids Res. 2014;42(5):3152–3163.
  • Zhang Y, Mandava CS, Cao W, et al. HflX is a ribosome-splitting factor rescuing stalled ribosomes under stress conditions. Nat Struct Mol Biol. 2015;22(11):906–913.
  • Bennison DG, Irving SE, Corrigan RM. The impact of the stringent response on TRAFAC GTPases and prokaryotic ribosome assembly. Cells. 2019;8(11):1313–1324.
  • Srinivasan K, Dey S, Sengupta J. Structural modules of the stress-induced protein HflX: an outlook on its evolution and biological role. Curr Genet. 2019;65(2):363–370.
  • Rudra P, Hurst-Hess KR, Cotten KL, et al. Mycobacterial HflX is a ribosome splitting factor that mediates antibiotic resistance. Proc Natl Acad Sci USA. 2020;117(1):629–634.
  • Dey S, Biswas C, Sengupta J. The universally conserved GTPase HflX is an RNA helicase that restores heat-damaged Escherichia coli ribosomes. J Cell Biol. 2018;217(7):2519–2529.
  • Joazeiro CAP. Mechanisms and functions of ribosome-associated protein quality control. Nat Rev Mol Cell Biol. 2019;20(6):368–383.
  • Crowe-mcauliffe C, Takada H, Murina V, et al. Structural basis for bacterial ribosome-associated quality control by RqcH and RqcP. Mol Cell. 2021;81(1):115–117.
  • Brown A, Rathore S, Kimanius D, et al. Structures of the human mitochondrial ribosome in native states of assembly. Nat Struct Mol Biol. 2017;24(10):866–869.
  • Filbeck S, Cerullo F, Paternoga H, et al. Mimicry of canonical translation elongation underlies alanine tail synthesis in RQC. Mol Cell. 2021;81(1):104–106.
  • Kuroha K, Zinoviev A, Hellen CUT, et al. Release of ubiquitinated and non-ubiquitinated nascent chains from stalled mammalian ribosomal complexes by ANKZF1 and Ptrh1. Mol Cell. 2018;72(2):286–288.
  • Verma R, Reichermeier KM, Burroughs AM, et al. Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes. Nature. 2018;557(7705):446–451.
  • Duarte I, Nabuurs SB, Magno R, et al. Evolution and diversification of the organellar release factor family. Mol Biol Evol. 2012;29(11):3497–3512.
  • Feaga HA, Quickel MD, Hankey-Giblin PA, et al. Human cells require non-stop ribosome rescue activity in mitochondria. PLoS Genet. 2016;12(3):e1005964.
  • Richter R, Rorbach J, Pajak A, et al. A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. EMBO J. 2010;29(6):1116–1125.
  • Handa Y, Hikawa Y, Tochio N, et al. Solution structure of the catalytic domain of the mitochondrial protein ICT1 that is essential for cell vitality. J Mol Biol. 2010;404(2):260–273.
  • Akabane S, Ueda T, Nierhaus KH, et al. Ribosome rescue and translation termination at non-standard stop codons by ICT1 in mammalian mitochondria. PLoS Genet. 2014;10(9):e1004616.
  • van Belzen N, Diesveld MP, van der Made AC, et al. Identification of mRNAs that show modulated expression during colon carcinoma cell differentiation. Eur J Biochem. 1995;234(3):843–848.
  • Chang W, Yu Z, Tian M, et al. Immature colon carcinoma transcript-1 promotes cell growth of hepatocellular carcinoma via facilitating cell cycle progression and apoptosis resistance. Oncol Rep. 2017;38(6):3489–3496.
  • Antonicka H, Ostergaard E, Sasarman F, et al. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. Am J Hum Genet. 2010;87(1):115–122.
  • Gopalakrishna S, Pearce SF, Dinan AM, et al. C6orf203 is an RNA-binding protein involved in mitochondrial protein synthesis. Nucleic Acids Res. 2019;47(17):9386–9399.
  • Kotrys AV, Cysewski D, Czarnomska SD, et al. Quantitative proteomics revealed C6orf203/MTRES1 as a factor preventing stress-induced transcription deficiency in human mitochondria. Nucleic Acids Res. 2019;47(14):7502–7517.
  • Perrone E, Cavole TR, Oliveira MG, et al. Leigh syndrome in a patient with a novel C12orf65 pathogenic variant: case report and literature review. Genet Mol Biol. 2020;43(2):e20180271.
  • Nishihara H, Omoto M, Takao M, et al. Autopsy case of the C12orf65 mutation in a patient with signs of mitochondrial dysfunction. Neurol Genet. 2017;3(4):e171.
  • Spiegel R, Mandel H, Saada A, et al. Delineation of C12orf65-related phenotypes: a genotype-phenotype relationship. Eur J Hum Genet. 2014;22(8):1019–1025.
  • Heidary G, Calderwood L, Cox GF, et al. Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature. J Neuroophthalmol. 2014;34(1):39–43.
  • Lavdovskaia E, Denks K, Nadler F, et al. Dual function of GTPBP6 in biogenesis and recycling of human mitochondrial ribosomes. Nucleic Acids Res. 2020;48(22):12929–12942.
  • Hillen HS, Lavdovskaia E, Nadler F, et al. Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling. Nat Commun. 2021;12(1). DOI:10.1038/s41467-021-23702-y