Abstract
Despite its similarity to protein biosynthesis in bacteria, translation in the mitochondria of modern eukaryotes has several unique features, such as the necessity for coordination of translation of mitochondrial mRNAs encoding proteins of the electron transport chain complexes with translation of other protein components of these complexes in the cytosol. In the mitochondria of baker’s yeast Saccharomyces cerevisiae, this coordination is carried out by a system of translational activators that predominantly interact with the 5′-untranslated regions of mitochondrial mRNAs. No such system has been found in human mitochondria, except a single identified translational activator, TACO1. Here, we studied the role of the ZMYND17 gene, an ortholog of the yeast gene for the translational activator Mss51p, on the mitochondrial translation in human cells. Deletion of the ZMYND17 gene did not affect translation in the mitochondria, but led to the decrease in the cytochrome c oxidase activity and increase in the amount of free F1 subunit of ATP synthase. We also investigated the evolutionary history of Mss51p and ZMYND17 and suggested a possible mechanism for the divergence of functions of these orthologous proteins.
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Abbreviations
- 5′-UTR:
-
5′-untranslated region
- CIV:
-
cytochrome c oxidase complex IV
References
Lazcano, A., and Peretó, J. (2021) Prokaryotic symbiotic consortia and the origin of nucleated cells: a critical review of Lynn Margulis hypothesis, BioSystems, 204, 104408, https://doi.org/10.1016/j.biosystems.2021.104408.
Levitskii, S. A., Baleva, M. V., Chicherin, I. V., Krasheninnikov, I. A., and Kamenski, P. A. (2020) Protein biosynthesis in mitochondria: past simple, present perfect, future indefinite, Biochemistry (Moscow), 85, 257-263, https://doi.org/10.1134/S0006297920030013.
Kuzmenko, A. V., Levitskii, S. A., Vinogradova, E. N., Atkinson, G. C., Hauryliuk, V., et al. (2013) Protein biosynthesis in mitochondria, Biochemistry, 78, 855-866.
Al-Faresi, R. A. Z., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M. A. (2019) Mammalian mitochondrial translation-revealing consequences of divergent evolution, Biochem. Soc. Trans., 47, 1429-1436, https://doi.org/10.1042/BST20190265.
Foury, F., Roganti, T., Lecrenier, N., and Purnelle, B. (1998) The complete sequence of the mitochondrial genome of Saccharomyces cerevisiae, FEBS Lett., 440, 325-331, https://doi.org/10.1016/S0014-5793(98)01467-7.
Lipinski, K. A., Kaniak-Golik, A., and Golik, P. (2010) Maintenance and expression of the S. cerevisiae mitochondrial genome – from genetics to evolution and systems biology, Biochim. Biophys. Acta, 1797, 1086-1098, https://doi.org/10.1016/j.bbabio.2009.12.019.
Derbikova, K. S., Levitsky, S. A., Chicherin, I. V., Vinogradova, E. N., and Kamenski, P. A. (2018) Activation of yeast mitochondrial translation: who is in charge? Biochemistry (Moscow), 83, 87-97, https://doi.org/10.1134/S0006297918020013.
Zamudio-Ochoa, A., Camacho-Villasana, Y., García-Guerrero, A. E., Pérez-Martínez, X. (2014) The Pet309 pentatricopeptide repeat motifs mediate efficient binding to the mitochondrial COX1 transcript in yeast, RNA Biol., 11, 953-967, https://doi.org/10.4161/rna.29780.
Manthey, G. M., and McEwen, J. E. (1995) The product of the nuclear gene PET309 is required for translation of mature mRNA and stability or production of intron-containing RNAs derived from the mitochondrial COX1 locus of Saccharomyces cerevisiae, EMBO J., 14, 4031-4043, https://doi.org/10.1002/j.1460-2075.1995.tb00074.x.
Hillman, G. A., and Henry, M. F. (2019) The yeast protein Mam33 functions in the assembly of the mitochondrial ribosome, J. Biol. Chem., 294, 9813-9829, https://doi.org/10.1074/jbc.RA119.008476.
De Silva, D., Poliquin, S., Zeng, R., Zamudio-Ochoa, A., Marrero, N., et al. (2017) The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation, Nucleic Acids Res., 45, 6628-6643, https://doi.org/10.1093/nar/gkx426.
Perez-Martinez, X., Broadley, S. A., and Fox, T. D. (2003) Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly synthesized Cox1p, EMBO J., 22, 5951-5961, https://doi.org/10.1093/emboj/cdg566.
Perez-Martinez, X., Butler, C. A., Shingu-Vazquez, M., and Fox, T. D. (2009) Dual functions of Mss51 couple synthesis of Cox1 to assembly of cytochrome c oxidase in Saccharomyces cerevisiae mitochondria, Mol. Biol. Cell, 20, 4371-4380, https://doi.org/10.1091/mbc.E09-06-0522.
Soto, I. C., Fontanesi, F., Myers, R. S., Hamel, P., and Barrientos, A. (2012) A heme-sensing mechanism in the translational regulation of mitochondrial cytochrome c oxidase biogenesis, Cell Metab., 16, 801-813, https://doi.org/10.1016/j.cmet.2012.10.018.
Khalimonchuk, O., Bestwick, M., Meunier, B., Watts, T. C., and Winge, D. R. (2010) Formation of the redox cofactor centers during cox1 maturation in yeast cytochrome oxidase, Mol. Cell. Biol., 30, 1004-1017, https://doi.org/10.1128/mcb.00640-09.
Scheffler, I. E. (2007) Mitochondria: Second Edition, John Wiley and Sons, https://doi.org/10.1002/9780470191774.
Gissi, C., Iannelli, F., and Pesole, G. (2008) Evolution of the mitochondrial genome of Metazoa as exemplified by comparison of congeneric species, Heredity (Edinb), 101, 301-320, https://doi.org/10.1038/hdy.2008.62.
Christian, B. E., Spremulli, L. L. (2010) Preferential selection of the 5′-terminal start codon on leaderless mRNAs by mammalian mitochondrial ribosomes, J. Biol. Chem., 285, 28379-28386, https://doi.org/10.1074/jbc.M110.149054.
Kummer, E., Leibundgut, M., Rackham, O., Lee, R. G., Boehringer, D., et al. (2018) Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM, Nature, 560, 263-267, https://doi.org/10.1038/s41586-018-0373-y.
Jones, C. N., Wilkinson, K. A., Hung, K. T., Weeks, K. M., and Spremulli, L. L. (2008) Lack of secondary structure characterizes the 5′-ends of mammalian mitochondrial mRNAs, RNA, 14, 862-871, https://doi.org/10.1261/rna.909208.
Weraarpachai, W., Antonicka, H., Sasarman, F., Seeger, J., Schrank, B., et al. (2009) Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome, Nat. Genet., 41, 833-837, https://doi.org/10.1038/ng.390.
Richman, T. R., Spahr, H., Ermer, J. A., Davies, S. M. K., Viola, H. M., et al. (2016) Loss of the RNA-binding protein TACO1 causes late-onset mitochondrial dysfunction in mice, Nat. Commun., 7, 11884, https://doi.org/10.1038/ncomms11884.
Sferruzza, G., Del Bondio, A., Citterio, A., Vezzulli, P., Guerrieri, S., et al. (2021) U-fiber leukoencephalopathy due to a novel mutation in the TACO1 gene, Neurol. Genet., 7, e573, https://doi.org/10.1212/nxg.0000000000000573.
Szklarczyk, R., Wanschers, B. F. J., Cuypers, T. D., Esseling, J. J., Riemersma, M., et al. (2012) Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase, Genome Biol., 13, R12, https://doi.org/10.1186/gb-2012-13-2-r12.
Moyer, A. L., and Wagner, K. R. (2015) Mammalian Mss51 is a skeletal muscle-specific gene modulating cellular metabolism, J. Neuromuscul. Dis., 2, 371-385, https://doi.org/10.3233/JND-150119.
Fujita, R., Yoshioka, K., Seko, D., Suematsu, T., Mitsuhashi, S., et al. (2018) Zmynd17 controls muscle mitochondrial quality and whole-body metabolism, FASEB J., 32, 5012-5025, https://doi.org/10.1096/fj.201701264R.
Rovira Gonzalez, Y. I., Moyer, A. L., LeTexier, N. J., Bratti, A. D., Feng, S., et al. (2019) Mss51 deletion enhances muscle metabolism and glucose homeostasis in mice, JCI Insight, 4, e122247, https://doi.org/10.1172/jci.insight.122247.
Rovira Gonzalez, Y. I., Moyer, A. L., LeTexier, N. J., Bratti, A. D., Feng, S., et al. (2021) Mss51 deletion increases endurance and ameliorates histopathology in the mdx mouse model of Duchenne muscular dystrophy, FASEB J., 35, e21276, https://doi.org/10.1096/fj.202002106RR.
Chicherin, I. V., Baleva, M. V., Levitskii, S. A., Dashinimaev, E. B., Krasheninnikov, I. A., and Kamenski, P. (2020) Initiation factor 3 is dispensable for mitochondrial translation in cultured human cells, Sci. Rep., 10, 7110, https://doi.org/10.1038/s41598-020-64139-5.
Shan, Q., Wang, Y., Li, J., Zhang, Y., Chen, K., et al. (2013) Targeted genome modification of crop plants using a CRISPR-Cas system, Nat. Biotechnol., 31, 686-688, https://doi.org/10.1038/nbt.2650.
Wittig, I., Braun, H.-P., and Schägger, H. (2006) Blue native PAGE, Nat. Protoc., 1, 418-428, https://doi.org/10.1038/nprot.2006.62.
Jha, P., Wang, X., Auwerx, J. (2016) Analysis of mitochondrial respiratory chain supercomplexes using blue native polyacrylamide gel electrophoresis (BN-PAGE), in Curr. Protoc. Mouse Biol., John Wiley & Sons, Inc., Hoboken, NJ, USA, pp. 1-14, https://doi.org/10.1002/9780470942390.mo150182.
Schafer, E., Seelert, H., Reifschneider, N. H., Krause, F., Dencher, N. A., and Vonck, J. (2006) Architecture of active mammalian respiratory chain supercomplexes, J. Biol. Chem., 281, 15370-15375, https://doi.org/10.1074/jbc.M513525200.
Kuzmenko, A., Atkinson, G. C., Levitskii, S., Zenkin, N., Tenson, T., et al. (2014) Mitochondrial translation initiation machinery: conservation and diversification, Biochimie, 100, 132-140, https://doi.org/10.1016/j.biochi.2013.07.024.
Herrmann, J. M., Woellhaf, M. W., and Bonnefoy, N. (2013) Control of protein synthesis in yeast mitochondria: the concept of translational activators, Biochim. Biophys. Acta, 1833, 286-294, https://doi.org/10.1016/j.bbamcr.2012.03.007.
Acknowledgments
Scientific equipment used in this work was purchased through the Moscow State University Development program. The authors of this study are members of the Scientific and Education School “Molecular technologies of live systems and synthetic biology” at the Moscow State University.
Funding
This work was supported by the Russian Foundation for Basic Research (project no. 18-29-07002; experimental studies) and the State Budget Project of the Moscow State University 24-2-21 (bioinformatics studies).
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Baleva, M.V., Piunova, U.E., Chicherin, I.V. et al. Yeast Translational Activator Mss51p and Human ZMYND17 – Two Proteins with a Common Origin, but Different Functions. Biochemistry Moscow 86, 1151–1161 (2021). https://doi.org/10.1134/S0006297921090108
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DOI: https://doi.org/10.1134/S0006297921090108