The TOM complex from an evolutionary perspective and the functions of TOMM70

Metin Özdemir; Sven Dennerlein

doi:10.1515/hsz-2024-0043

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Article

The TOM complex from an evolutionary perspective and the functions of TOMM70

Metin Özdemir

Metin Özdemir studied molecular biology and genetics as well as physics at Bogazici University, Istanbul. He shortly studied plant development at Dahlem Center of Plant Sciences, Berlin. He later focused on olfactory receptor selection mechanisms in zebrafish model organisms as part of his MSc studies at Bogazici University. In late 2019, he started his doctoral studies at Universitätsmedizin Göttingen (UMG) on mitochondrial protein biogenesis and quality control and completed his doctoral studies in November 2023. Currently, he is continuing his work as a postdoctoral researcher at UMG.
and Sven Dennerlein

Sven Dennerlein studied Molecular Biotechnology at the Technical University in Dresden and obtained his PhD at the Newcastle University with a main focus in mitochondrial translation. From 2010 on he worked as a postdoctoral fellow in the Department of Cellular Biochemistry, University Medical Center Göttingen. Since 2020 he is a group leader in Department of Cellular Biochemistry, University Medical Center Göttingen with the focus on mitochondrial biochemistry and metabolism within eukaryotic cells. In this regard he is especially interested how mitochondria communicate with other cell organelles and how these networks are in communication with each other.

Published/Copyright: August 2, 2024

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From the journal Biological Chemistry Volume 405 Issue 9-10

Abstract

In humans, up to 1,500 mitochondrial precursor proteins are synthesized at cytosolic ribosomes and must be imported into the organelle. This is not only essential for mitochondrial but also for many cytosolic functions. The majority of mitochondrial precursor proteins are imported over the translocase of the outer membrane (TOM). In recent years, high-resolution structure analyses from different organisms shed light on the composition and arrangement of the TOM complex. Although significant similarities have been found, differences were also observed, which have been favored during evolution and could reflect the manifold functions of TOM with cellular signaling and its response to altered metabolic situations. A key component within these regulatory mechanisms is TOMM70, which is involved in protein import, forms contacts to the ER and the nucleus, but is also involved in cellular defense mechanisms during infections.

Keywords: mitochondria; mitochondrial import; TOM complex

Corresponding author: Sven Dennerlein, Institute for Cellular Biochemistry, University Medical Center Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany, E-mail: sven.dennerlein@med.uni-goettingen.de

Funding source: Ministry of Science and Culture of Lower Saxony and Volkswagen Foundation

Award Identifier / Grant number: 762-12-9/19 (ZN3457)

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: A06(PR) (SFB1286)

About the authors

Metin Özdemir

Metin Özdemir studied molecular biology and genetics as well as physics at Bogazici University, Istanbul. He shortly studied plant development at Dahlem Center of Plant Sciences, Berlin. He later focused on olfactory receptor selection mechanisms in zebrafish model organisms as part of his MSc studies at Bogazici University. In late 2019, he started his doctoral studies at Universitätsmedizin Göttingen (UMG) on mitochondrial protein biogenesis and quality control and completed his doctoral studies in November 2023. Currently, he is continuing his work as a postdoctoral researcher at UMG.

Sven Dennerlein

Sven Dennerlein studied Molecular Biotechnology at the Technical University in Dresden and obtained his PhD at the Newcastle University with a main focus in mitochondrial translation. From 2010 on he worked as a postdoctoral fellow in the Department of Cellular Biochemistry, University Medical Center Göttingen. Since 2020 he is a group leader in Department of Cellular Biochemistry, University Medical Center Göttingen with the focus on mitochondrial biochemistry and metabolism within eukaryotic cells. In this regard he is especially interested how mitochondria communicate with other cell organelles and how these networks are in communication with each other.

Acknowledgments

This research project was supported by the International Max Planck Research School for Genome Science (MÖ).

Research ethics: Not applicable.
Author contributions: MÖ and SD designed the figures and wrote the manuscript.
Competing interests: No competing interests.
Research funding: This research project was funded by the Ministry of Science and Culture of Lower Saxony and Volkswagen Foundation No. 762-12-9/19 (ZN3457) (to S.D.) and the Sonderforschungsbereich (SFB)1,286 (project A06(PR)).
Data availability: Not applicable.

References

Abe, Y., Shodai, T., Muto, T., Mihara, K., Torii, H., Nishikawa, S.ichi, Endo, T., and Kohda, D. (2000). Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100: 551–560, https://doi.org/10.1016/S0092-8674(00)80691-1.Search in Google Scholar

Ahting, U., Thun, C., Hegerl, R., Typke, D., Nargang, F.E., Neupert, W., and Nussberger, S. (1999). The TOM core complex: the general protein import pore of the outer membrane of mitochondria. J. Cell Biol. 147: 959–968, https://doi.org/10.1083/jcb.147.5.959.Search in Google Scholar

Araiso, Y., Imai, K., and Endo, T. (2021). Structural snapshot of the mitochondrial protein import gate. FEBS J. 288: 5300–5310, https://doi.org/10.1111/febs.15661.Search in Google Scholar

Araiso, Y., Imai, K., and Endo, T. (2022). Role of the TOM complex in protein import into mitochondria: structural views. Annu. Rev. Biochem. 91: 679–703, https://doi.org/10.1146/annurev-biochem-032620-104527.Search in Google Scholar

Araiso, Y., Tsutsumi, A., Qiu, J., Imai, K., Shiota, T., Song, J., Lindau, C., Wenz, L.S., Sakaue, H., Yunoki, K., et al.. (2019). Structure of the mitochondrial import gate reveals distinct preprotein paths. Nature 575: 395–401, https://doi.org/10.1038/s41586-019-1680-7.Search in Google Scholar

Backes, S., Bykov, Y.S., Flohr, T., Räschle, M., Zhou, J., Lenhard, S., Krämer, L., Mühlhaus, T., Bibi, C., Jann, C., et al.. (2021). The chaperone-binding activity of the mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress. Cell Rep. 35, https://doi.org/10.1016/j.celrep.2021.108936.Search in Google Scholar

Backes, S., Hess, S., Boos, F., Woellhaf, M.W., Gödel, S., Jung, M., Mühlhaus, T., and Herrmann, J.M. (2018). Tom70 enhances mitochondrial preprotein import efficiency by binding to internal targeting sequences. J. Cell Biol. 217: 1369–1382, https://doi.org/10.1083/jcb.201708044.Search in Google Scholar

Bausewein, T., Naveed, H., Liang, J., and Nussberger, S. (2020). The structure of the TOM core complex in the mitochondrial outer membrane. Biol. Chem. 401: 687–697, https://doi.org/10.1515/hsz-2020-0104.Search in Google Scholar

Bhowal, C., Ghosh, S., Ghatak, D., and De, R. (2023). Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight. Mol. Cell. Biochem. 478: 1325–1343, https://doi.org/10.1007/s11010-022-04593-z.Search in Google Scholar

Bojkova, D., Klann, K., Koch, B., Widera, M., Krause, D., Ciesek, S., Cinatl, J., and Münch, C. (2020). Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature 583: 469–472, https://doi.org/10.1038/s41586-020-2332-7.Search in Google Scholar

Brandherm, L., Kobaš, A.M., Klöhn, M., Brüggemann, Y., Pfaender, S., Rassow, J., and Kreimendahl, S. (2021). Phosphorylation of sars-cov-2 orf9b regulates its targeting to two binding sites in tom70 and recruitment of hsp90. Int. J. Mol. Sci. 22: 1–19, https://doi.org/10.3390/ijms22179233.Search in Google Scholar

Brix, J., Ziegler, G.A., Dietmeier, K., Schneider-Mergener, J., Schulz, G.E., and Pfanner, N. (2000). The mitochondrial import receptor Tom70: identification of a 25 kDa core domain with a specific binding site for preproteins. J. Mol. Biol. 303: 479–488, https://doi.org/10.1006/jmbi.2000.4120.Search in Google Scholar

Chang, X., Ismail, N.I., Rahman, A., Xu, D., Chan, R.W.Y., Ong, S.-G., and Ong, S.-B. (2023). Long COVID-19 and the heart: Is cardiac mitochondria the missing link? Antioxid. Redox Signaling 38: 599–618, https://doi.org/10.1089/ars.2022.0126.Search in Google Scholar

Chen, C.-Y., Ping, Y.-H., Lee, H.-C., Chen, K.-H., Lee, Y.-M., Chan, Y.-J., Lien, T.-C., Jap, T.-S., Lin, C.-H., Kao, L.-S., et al.. (2007). Open reading frame 8a of the human severe acute respiratory syndrome coronavirus not only promotes viral replication but also induces apoptosis. J. Infect. Dis. 196: 405–415, https://doi.org/10.1086/519166.Search in Google Scholar

Dekker, P.J.T., Ryan, M.T., Brix, J., Müller, H., Hönlinger, A., and Pfanner, N. (1998). Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Mol. Cell. Biol. 18: 6515–6524, https://doi.org/10.1128/mcb.18.11.6515.Search in Google Scholar

Denaro, C.A., Haloush, Y.I., Hsiao, S.Y., Orgera, J.J., Osorio, T., Riggs, L.M., Sassaman, J.W., Williams, S.A., Monte Carlo, A.R., Da Costa, R.T., et al.. (2022). COVID‐19 and neurodegeneration: the mitochondrial connection. Aging Cell 21, https://doi.org/10.1111/acel.13727.Search in Google Scholar

den Brave, F., Pfanner, N., and Becker, T. (2023). Mitochondrial entry gate as regulatory hub. Biochim. Biophys. Acta Mol. Cell Res. 1871: 119529, https://doi.org/10.1016/j.bbamcr.2023.119529.Search in Google Scholar

Derré, I., Swiss, R., and Agaisse, H. (2011). The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS Pathog. 7, https://doi.org/10.1371/journal.ppat.1002092.Search in Google Scholar

Dewar, C.E., Oeljeklaus, S., Mani, J., Mühlhäuser, W.W.D., von Känel, C., Zimmermann, J., Ochsenreiter, T., Warscheid, B., and Schneider, A. (2022). Mistargeting of aggregation prone mitochondrial proteins activates a nucleus-mediated posttranscriptional quality control pathway in trypanosomes. Nat. Commun. 13, https://doi.org/10.1038/s41467-022-30748-z.Search in Google Scholar

Dolezal, P., Likic, V., Tachezy, J., and Lithgow, T. (2006). Evolution of the molecular machines for protein import into mitochondria. Science 313: 314–318, https://doi.org/10.1126/science.1127895.Search in Google Scholar

Eisenberg-Bord, M., Zung, N., Collado, J., Drwesh, L., Fenech, E.J., Fadel, A., Dezorella, N., Bykov, Y.S., Rapaport, D., Fernandez-Busnadiego, R., et al.. (2021). CNM1 mediates nucleus–mitochondria contact site formation in response to phospholipid levels. J. Cell Biol. 220, https://doi.org/10.1083/jcb.202104100.Search in Google Scholar

Filadi, R., Leal, N.S., Schreiner, B., Rossi, A., Dentoni, G., Pinho, C.M., Wiehager, B., Cieri, D., Calì, T., Pizzo, P., et al.. (2018). TOM70 sustains cell bioenergetics by promoting IP3R3-mediated ER to mitochondria Ca2+ transfer. Curr. Biol. 28: 369–382.e6, https://doi.org/10.1016/j.cub.2017.12.047.Search in Google Scholar

Fu, Y.Z., Wang, S.Y., Zheng, Z.Q., Yi, Huang, Li, W.W., Xu, Z.S., and Wang, Y.Y. (2021). SARS-CoV-2 membrane glycoprotein M antagonizes the MAVS-mediated innate antiviral response. Cell. Mol. Immunol. 18: 613–620, https://doi.org/10.1038/s41423-020-00571-x.Search in Google Scholar

Ganji, R. and Reddy, P.H. (2021). Impact of COVID-19 on mitochondrial-based immunity in aging and age-related diseases. Front. Aging Neurosci. 12, https://doi.org/10.3389/fnagi.2020.614650.Search in Google Scholar

Gao, X., Zhu, K., Qin, B., Olieric, V., Wang, M., and Cui, S. (2021). Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions. Nat. Commun. 12: 2843, https://doi.org/10.1038/s41467-021-23118-8.Search in Google Scholar

Gibellini, L., De Biasi, S., Paolini, A., Borella, R., Boraldi, F., Mattioli, M., Lo Tartaro, D., Fidanza, L., Caro‐Maldonado, A., Meschiari, M., et al.. (2020). Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia. EMBO Mol. Med. 12, https://doi.org/10.15252/emmm.202013001.Search in Google Scholar

Goddard, T.D., Huang, C.C., Meng, E.C., Pettersen, E.F., Couch, G.S., Morris, J.H., and Ferrin, T.E. (2018). UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27: 14–25, https://doi.org/10.1002/pro.3235.Search in Google Scholar

Gomkale, R., Cruz-Zaragoza, L.D., Suppanz, I., Guiard, B., Montoya, J., Callegari, S., Pacheu-Grau, D., Warscheid, B., and Rehling, P. (2020). Defining the substrate spectrum of the TIM22 complex identifies pyruvate carrier subunits as unconventional cargos. Curr. Biol. 30: 1119–1127.e5, https://doi.org/10.1016/j.cub.2020.01.024.Search in Google Scholar

Gordon, D.E., Hiatt, J., Bouhaddou, M., Rezelj, V.V., Ulferts, S., Braberg, H., Jureka, A.S., Obernier, K., Guo, J.Z., Batra, J., et al.. (2020a). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science 370, https://doi.org/10.1126/science.abe9403.Search in Google Scholar

Gordon, D.E., Jang, G.M., Bouhaddou, M., Xu, J., Obernier, K., White, K.M., O’Meara, M.J., Rezelj, V.V., Guo, J.Z., Swaney, D.L., et al.. (2020b). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583: 459–468, https://doi.org/10.1038/s41586-020-2286-9.Search in Google Scholar

Gray, M.W., Burger, G., and Lang, B.F. (1999). Mitochondrial evolution. Science 283: 1476–1481, https://doi.org/10.1126/science.283.5407.1476.Search in Google Scholar

Guan, Z., Yan, L., Wang, Q., Qi, L., Hong, S., Gong, Z., Yan, C., and Yin, P. (2021). Structural insights into assembly of human mitochondrial translocase TOM complex. Cell Discov. 7: 4–8, https://doi.org/10.1038/s41421-021-00252-7.Search in Google Scholar

Guna, A., Stevens, T.A., Inglis, A.J., Replogle, J.M., Esantsi, T.K., Muthukumar, G., Shaffer, K.C.L., Wang, M.L., Pogson, A.N., Jones, J.J., et al.. (2022). MTCH2 is a mitochondrial outer membrane protein insertase. Science 378: 317–322, https://doi.org/10.1126/science.add1856.Search in Google Scholar

Hartl, F.U. (1996). Molecular chaperones in cellular protein folding. Nature 381: 571–580, https://doi.org/10.1038/381571a0.Search in Google Scholar

Hossain, A., Akter, S., Rashid, A.A., Khair, S., and Alam, A.S.M.R.U. (2022). Unique mutations in SARS-CoV-2 Omicron subvariants’ non-spike proteins: potential impacts on viral pathogenesis and host immune evasion. Microb. Pathog. 170: 105699, https://doi.org/10.1016/j.micpath.2022.105699.Search in Google Scholar

Jacobs, J.L. and Coyne, C.B. (2013). Mechanisms of MAVS regulation at the mitochondrial membrane. J. Mol. Biol. 425: 5009–5019, https://doi.org/10.1016/j.jmb.2013.10.007.Search in Google Scholar

Jiang, H., Zhang, H., Meng, Q., Xie, J., Li, Y., Chen, H., Zheng, Y., Wang, X., Qi, H., Zhang, J., et al.. (2020). SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cell. Mol. Immunol. 17: 998–1000, https://doi.org/10.1038/s41423-020-0514-8.Search in Google Scholar

Jin, X., Sun, X., Chai, Y., Bai, Y., Li, Y., Hao, T., Qi, J., Song, H., Wong, C.C.L., and Gao, G.F. (2023). Structural characterization of SARS-CoV-2 dimeric ORF9b reveals potential fold-switching trigger mechanism. Sci. China Life Sci. 66: 152–164, https://doi.org/10.1007/s11427-022-2168-8.Search in Google Scholar

Johnston, A.J., Hoogenraad, J., Dougan, D.A., Truscott, K.N., Yano, M., Mori, M., Hoogenraad, N.J., and Ryan, M.T. (2002). Insertion and assembly of human Tom7 into the preprotein translocase complex of the outer mitochondrial membrane. J. Biol. Chem. 277: 42197–42204, https://doi.org/10.1074/jbc.M205613200.Search in Google Scholar

Kasahara, A. and Scorrano, L. (2014). Mitochondria: from cell death executioners to regulators of cell differentiation. Trends Cell Biol. 24: 761–770, https://doi.org/10.1016/j.tcb.2014.08.005.Search in Google Scholar

Kato, H. and Mihara, K. (2008). Identification of Tom5 and Tom6 in the preprotein translocase complex of human mitochondrial outer membrane. Biochem. Biophys. Res. Commun. 369: 958–963, https://doi.org/10.1016/j.bbrc.2008.02.150.Search in Google Scholar

Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K.J., Takeuchi, O., and Akira, S. (2005). IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 6: 981–988, https://doi.org/10.1038/ni1243.Search in Google Scholar

Ku, C., Nelson-Sathi, S., Roettger, M., Sousa, F.L., Lockhart, P.J., Bryant, D., Hazkani-Covo, E., McInerney, J.O., Landan, G., and Martin, W.F. (2015). Endosymbiotic origin and differential loss of eukaryotic genes. Nature 524: 427–432, https://doi.org/10.1038/nature14963.Search in Google Scholar

Kuhn, S., Bussemer, J., Chigri, F., and Vothknecht, U.C. (2009). Calcium depletion and calmodulin inhibition affect the import of nuclear-encoded proteins into plant mitochondria. Plant J. 58: 694–705, https://doi.org/10.1111/j.1365-313X.2009.03810.x.Search in Google Scholar

Kulawiak, B., Höpker, J., Gebert, M., Guiard, B., Wiedemann, N., and Gebert, N. (2013). The mitochondrial protein import machinery has multiple connections to the respiratory chain. Biochim. Biophys. Acta – Bioenerg. 1827: 612–626, https://doi.org/10.1016/j.bbabio.2012.12.004.Search in Google Scholar

Kuszak, A.J., Jacobs, D., Gurnev, P.A., Shiota, T., Louis, J.M., Lithgow, T., Bezrukov, S.M., Rostovtseva, T.K., and Buchanan, S.K. (2015). Evidence of distinct channel conformations and substrate binding affinities for the mitochondrial outer membrane protein translocase pore Tom40. J. Biol. Chem. 290: 26204–26217, https://doi.org/10.1074/jbc.M115.642173.Search in Google Scholar

Latorre-Muro, P., O’Malley, K.E., Bennett, C.F., Perry, E.A., Balsa, E., Tavares, C.D.J., Jedrychowski, M., Gygi, S.P., and Puigserver, P. (2021). A cold-stress-inducible PERK/OGT axis controls TOM70-assisted mitochondrial protein import and cristae formation. Cell Metab. 33: 598–614.e7, https://doi.org/10.1016/j.cmet.2021.01.013.Search in Google Scholar

Lenhard, S., Gerlich, S., Khan, A., Rödl, S., Bökenkamp, J.E., Peker, E., Zarges, C., Faust, J., Storchova, Z., Räschle, M., et al.. (2023). The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis. J. Cell Biol. 222, https://doi.org/10.1083/jcb.202303002.Search in Google Scholar

Letunic, I. and Bork, P. (2021). Interactive Tree of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49: W293–W296, https://doi.org/10.1093/nar/gkab301.Search in Google Scholar

Li, X., Straub, J., Medeiros, T.C., Mehra, C., Den Brave, F., Peker, E., Atanassov, I., Stillger, K., Michaelis, J.B., Burbridge, E., et al.. (2022). Mitochondria shed their outer membrane in response to infection-induced stress. Science 375, https://doi.org/10.1126/science.abi4343.Search in Google Scholar

Liu, X.Y., Wei, B., Shi, H.X., Shan, Y.F., and Wang, C. (2010). Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. Cell Res. 20: 994–1011, https://doi.org/10.1038/cr.2010.103.Search in Google Scholar

Mani, J., Desy, S., Niemann, M., Chanfon, A., Oeljeklaus, S., Pusnik, M., Schmidt, O., Gerbeth, C., Meisinger, C., Warscheid, B., et al.. (2015). Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat. Commun. 6, https://doi.org/10.1038/ncomms7646.Search in Google Scholar

Mani, J., Meisinger, C., and Schneider, A. (2016). Peeping at TOMs—diverse entry gates to mitochondria provide insights into the evolution of Eukaryotes. Mol. Biol. Evol. 33: 337–351, https://doi.org/10.1093/molbev/msv219.Search in Google Scholar

Margulis, L. (1967). On the origin of mitosing cells. J. Theor. Biol. 14: 255–274, https://doi.org/10.1016/0022-5193(67)90079-3, http://www.ncbi.nlm.nih.gov/pubmed/11541390.Search in Google Scholar

Margulis, L. (1970). Origin of eukaryotic cells: evidence and research implications for a theory of the origin and evolution of microbial. In: Plant, and animal cells on the Precambrian Earth. Hartford, Connecticut: Yale University Press, Connecticut Printers, Inc. Available at: https://books.google.de/books?id=mrBzQgAACAAJ.Search in Google Scholar

Margulis, L. (1991) Symbiosis in evolution: origins of cell motility. In: Osawa, S., and Honjo, T. (Eds.). Evolution of life: fossils, molecules, and culture. Springer, Japan, pp. 305–324.10.1007/978-4-431-68302-5_19Search in Google Scholar

McWhirter, S.M., TenOever, B.R., and Maniatis, T. (2005). Connecting mitochondria and innate immunity. Cell 122: 645–647, https://doi.org/10.1016/j.cell.2005.08.026.Search in Google Scholar

Melin, J., Kilisch, M., Neumann, P., Lytovchenko, O., Gomkale, R., Schendzielorz, A., Schmidt, B., Liepold, T., Ficner, R., Jahn, O., et al.. (2015). A presequence-binding groove in Tom70 supports import of Mdl1 into mitochondria. Biochim. Biophys. Acta – Mol. Cell Res. 1853: 1850–1859, https://doi.org/10.1016/j.bbamcr.2015.04.021.Search in Google Scholar

Melin, J., Schulz, C., Wrobel, L., Bernhard, O., Chacinska, A., Jahn, O., Schmidt, B., and Rehling, P. (2014). Presequence recognition by the Tom40 channel contributes to precursor translocation into the mitochondrial matrix. Mol. Cell. Biol. 34: 3473–3485, https://doi.org/10.1128/mcb.00433-14.Search in Google Scholar

Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., and Tschopp, J. (2005). Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437: 1167–1172, https://doi.org/10.1038/nature04193.Search in Google Scholar

Miserey‐Lenkei, S., Trajkovic, K., D’Ambrosio, J.M., Patel, A.J., Čopič, A., Mathur, P., Schauer, K., Goud, B., Albanèse, V., Gautier, R., et al.. (2021). A comprehensive library of fluorescent constructs of SARS‐CoV‐2 proteins and their initial characterisation in different cell types. Biol. Cell 113: 311–328, https://doi.org/10.1111/boc.202000158.Search in Google Scholar

Model, K., Meisinger, C., and Kühlbrandt, W. (2008). Cryo-electron microscopy structure of a yeast mitochondrial preprotein translocase. J. Mol. Biol. 383: 1049–1057, https://doi.org/10.1016/j.jmb.2008.07.087.Search in Google Scholar

Model, K., Prinz, T., Ruiz, T., Radermacher, M., Krimmer, T., Kühlbrandt, W., Pfanner, N., and Meisinger, C. (2002). Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex. J. Mol. Biol. 316: 657–666, https://doi.org/10.1006/jmbi.2001.5365.Search in Google Scholar

Moehlman, A.T. and Youle, R.J. (2020). Mitochondrial quality control and restraining innate immunity. Annu. Rev. Cell Dev. Biol. 36: 265–289, https://doi.org/10.1146/annurev-cellbio-021820-101354.Search in Google Scholar

Müller, M., Herrmann, A., Fujita, S., Uriu, K., Kruth, C., Strange, A., Kolberg, J.E., Schneider, M., Ito, J., Müller, M.A., et al.. (2023). ORF3c is expressed in SARS‐CoV‐2‐infected cells and inhibits innate sensing by targeting MAVS. EMBO Rep. 24, https://doi.org/10.15252/embr.202357137.Search in Google Scholar

Murley, A. and Nunnari, J. (2016). The emerging network of mitochondria-organelle contacts. Mol. Cell 61: 648–653, https://doi.org/10.1016/j.molcel.2016.01.031.Search in Google Scholar

Murley, A., Sarsam, R.D., Toulmay, A., Yamada, J., Prinz, W.A., and Nunnari, J. (2015). Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts. J. Cell Biol. 209: 539–548, https://doi.org/10.1083/jcb.201502033.Search in Google Scholar

Naito, T., Yang, H., Koh, D.H.Z., Mahajan, D., Lu, L., and Saheki, Y. (2023). Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites. Nat. Commun. 14, https://doi.org/10.1038/s41467-023-41213-w.Search in Google Scholar

Nguyen, N., Francoeur, N., Chartrand, V., Klarskov, K., Guillemette, G., and Boulay, G. (2009). Insulin promotes the association of heat shock protein 90 with the inositol 1,4,5-trisphosphate receptor to dampen its Ca2+ release activity. Endocrinology 150: 2190–2196, https://doi.org/10.1210/en.2008-1167.Search in Google Scholar

O’Neil, P.K., Richardson, L.G.L., Paila, Y.D., Piszczek, G., Chakravarthy, S., Noinaj, N., and Schnell, D. (2017). The POTRA domains of Toc75 exhibit chaperone-like function to facilitate import into chloroplasts. Proc. Natl. Acad. Sci. U. S. A. 114: E4868–E4876, https://doi.org/10.1073/pnas.1621179114.Search in Google Scholar

Ornelas, P., Bausewein, T., Martin, J., Morgner, N., Nussberger, S., and Kühlbrandt, W. (2023) Two conformations of the Tom20 preprotein receptor in the TOM holo complex. Proc. Natl. Acad. Sci. U. S. A. 120: 2017, https://doi.org/10.1073/pnas.2301447120.Search in Google Scholar

Paik, S., Kim, J.K., Silwal, P., Sasakawa, C., and Jo, E.K. (2021). An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell. Mol. Immunol. 18: 1141–1160, https://doi.org/10.1038/s41423-021-00670-3.Search in Google Scholar

Panchy, N., Lehti-Shiu, M., and Shiu, S.H. (2016). Evolution of gene duplication in plants. Plant Physiol. 171: 2294–2316, https://doi.org/10.1104/pp.16.00523.Search in Google Scholar

Panigrahi, R., Whelan, J., and Vrielink, A. (2014). Exploring ligand recognition, selectivity and dynamics of TPR domains of chloroplast Toc64 and mitochondria Om64 from Arabidopsis thaliana. J. Mol. Recognit. 27: 402–414, https://doi.org/10.1002/jmr.2360.Search in Google Scholar

Pettersen, E.F., Goddard, T.D., Huang, C.C., Meng, E.C., Couch, G.S., Croll, T.I., Morris, J.H., and Ferrin, T.E. (2021). UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30: 70–82, https://doi.org/10.1002/pro.3943.Search in Google Scholar

Pfanner, N., Warscheid, B., and Wiedemann, N. (2019). Mitochondrial proteins: from biogenesis to functional networks. Nat. Rev. Mol. Cell Biol. 20: 267–284, https://doi.org/10.1038/s41580-018-0092-0.Search in Google Scholar

Rout, S., Oeljeklaus, S., Makki, A., Tachezy, J., Warscheid, B., and Schneider, A. (2021). Determinism and contingencies shaped the evolution of mitochondrial protein import. Proc. Natl. Acad. Sci. U. S. A. 118: https://doi.org/10.1073/pnas.2017774118.Search in Google Scholar

Schmitt, S., Ahting, U., Eichacker, L., Granvogl, B., Go, N.E., Nargang, F.E., Neupert, W., and Nussberger, S. (2005). Role of Tom5 in maintaining the structural stability of the TOM complex of mitochondria. J. Biol. Chem. 280: 14499–14506, https://doi.org/10.1074/jbc.M413667200.Search in Google Scholar

Schneider, A. (2020). Evolution of mitochondrial protein import – lessons from trypanosomes. Biol. Chem. 401: 663–676, https://doi.org/10.1515/hsz-2019-0444.Search in Google Scholar

Seth, R.B., Sun, L., Ea, C.K., and Chen, Z.J. (2005). Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3. Cell 122: 669–682, https://doi.org/10.1016/j.cell.2005.08.012.Search in Google Scholar

Sharma, A., Kontodimas, K., and Bosmann, M. (2021). The MAVS immune recognition pathway in viral infection and sepsis. Antioxidants Redox Signal. 35: 1376–1392, https://doi.org/10.1089/ars.2021.0167.Search in Google Scholar

Shi, C.-S., Qi, H.-Y., Boularan, C., Huang, N.-N., Abu-Asab, M., Shelhamer, J.H., and Kehrl, J.H. (2014a). SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J. Immunol. 193: 3080–3089, https://doi.org/10.4049/jimmunol.1303196.Search in Google Scholar

Shi, C.-S., Qi, H.-Y., Boularan, C., Huang, N.-N., Abu-Asab, M., Shelhamer, J.H., and Kehrl, J.H. (2014b). SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J. Immunol. 193: 3080–3089, https://doi.org/10.4049/jimmunol.1303196.Search in Google Scholar

Shiota, T., Imai, K., Qiu, J., Hewitt, V.L., Tan, K., Shen, H.H., Sakiyama, N., Fukasawa, Y., Hayat, S., Kamiya, M., et al.. (2015). Molecular architecture of the active mitochondrial protein gate. Science 349: 1544–1548, https://doi.org/10.1126/science.aac6428.Search in Google Scholar

Shoraka, S., Samarasinghe, A.E., Ghaemi, A., and Mohebbi, S.R. (2023). Host mitochondria: more than an organelle in SARS-CoV-2 infection. Front. Cell. Infect. Microbiol. 13: 1–15, https://doi.org/10.3389/fcimb.2023.1228275.Search in Google Scholar

Stukalov, A., Girault, V., Grass, V., Karayel, O., Bergant, V., Urban, C., Haas, D.A., Huang, Y., Oubraham, L., Wang, A., et al.. (2021). Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 594: 246–252, https://doi.org/10.1038/s41586-021-03493-4.Search in Google Scholar

Su, J., Liu, D., Yang, F., Zuo, M.Q., Li, C., Dong, M.Q., Sun, S., and Sui, S.F. (2022a). Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors. Proc. Natl. Acad. Sci. U. S. A. 119: 1–10, https://doi.org/10.1073/pnas.2200158119.Search in Google Scholar

Su, J., Liu, D., Yang, F., Zuo, M.Q., Li, C., Dong, M.Q., Sun, S., and Sui, S.F. (2022b). Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors. Proc. Natl. Acad. Sci. U. S. A. 119: 1–10, https://doi.org/10.1073/pnas.2200158119.Search in Google Scholar

Surendran, H., Kumar, S., Narasimhaiah, S., Ananthamurthy, A., Varghese, P., D’Souza, G.A., Medigeshi, G., and Pal, R. (2022). SARS‐CoV‐2 infection of human‐induced pluripotent stem cells‐derived lung lineage cells evokes inflammatory and chemosensory responses by targeting mitochondrial pathways. J. Cell. Physiol. 237: 2913–2928, https://doi.org/10.1002/jcp.30755.Search in Google Scholar

Thorne, L.G., Bouhaddou, M., Reuschl, A.-K., Zuliani-Alvarez, L., Polacco, B., Pelin, A., Batra, J., Whelan, M.V.X., Hosmillo, M., Fossati, A., et al.. (2022). Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature 602: 487–495, https://doi.org/10.1038/s41586-021-04352-y.Search in Google Scholar

Tiku, V., Tan, M.W., and Dikic, I. (2020). Mitochondrial functions in infection and immunity. Trends Cell Biol. 30: 263–275, https://doi.org/10.1016/j.tcb.2020.01.006.Search in Google Scholar

Timmis, J.N., Ayliff, M.A., Huang, C.Y., and Martin, W. (2004). Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat. Rev. Genet. 5: 123–135, https://doi.org/10.1038/nrg1271.Search in Google Scholar

Truscott, K.N., Brandner, K., and Pfanner, N. (2003). Mechanisms of protein import into mitochondria. Curr. Biol. 13: 326–337, https://doi.org/10.1016/S0960-9822(03)00239-2.Search in Google Scholar

Tucker, K. and Park, E. (2019). Cryo-EM structure of the mitochondrial protein-import channel TOM complex at near-atomic resolution. Nat. Struct. Mol. Biol. 26: 1158–1166, https://doi.org/10.1038/s41594-019-0339-2.Search in Google Scholar

Wang, W., Chen, X., Zhang, L., Yi, J., Ma, Q., Yin, J., Zhuo, W., Gu, J., and Yang, M. (2020). Atomic structure of human TOM core complex. Cell Discov. 6, https://doi.org/10.1038/s41421-020-00198-2.Search in Google Scholar

Wiedemann, N. and Pfanner, N. (2017). Mitochondrial machineries for protein import and assembly. Annu. Rev. Biochem. 86: 685–714, https://doi.org/10.1146/annurev-biochem-060815-014352.Search in Google Scholar

Wu, J., Shi, Y., Pan, X., Wu, S., Hou, R., Zhang, Y., Zhong, T., Tang, H., Du, W., Wang, L., et al.. (2021a). SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep. 34: 108761, https://doi.org/10.1016/j.celrep.2021.108761.Search in Google Scholar

Wu, J., Shi, Y., Pan, X., Wu, S., Hou, R., Zhang, Y., Zhong, T., Tang, H., Du, W., Wang, L., et al.. (2021b). SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO. Cell Rep. 34: 108761, https://doi.org/10.1016/j.celrep.2021.108761.Search in Google Scholar

Young, J.C., Hoogenraad, N.J., and Hartl, F.U. (2003). Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112: 41–50, https://doi.org/10.1016/S0092-8674(02)01250-3.Search in Google Scholar

Zachar, I. and Boza, G. (2020). Endosymbiosis before eukaryotes: mitochondrial establishment in protoeukaryotes. Cell. Mol. Life Sci. 77: 3503–3523, https://doi.org/10.1007/s00018-020-03462-6.Search in Google Scholar

Zanphorlin, L.M., Lima, T.B., Wong, M.J., Balbuena, T.S., Minetti, C.A.S.A., Remeta, D.P., Young, J.C., Barbosa, L.R.S., Gozzo, F.C., and Ramos, C.H.I. (2016). Heat shock protein 90 kDa (Hsp90) has a second functional interaction site with the mitochondrial import receptor Tom70. J. Biol. Chem. 291: 18620–18631, https://doi.org/10.1074/jbc.M115.710137.Search in Google Scholar

Zarsky, V., Tachezy, J., and Dolezal, P. (2012). Tom40 is likely common to all mitochondria. Curr. Biol. 22: R479–R481, https://doi.org/10.1016/j.cub.2012.03.057.Search in Google Scholar

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/hsz-2024-0043).

Received: 2024-03-15

Accepted: 2024-07-17

Published Online: 2024-08-02

Published in Print: 2024-10-28

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https://doi.org/10.1515/hsz-2024-0043

Keywords for this article

mitochondria; mitochondrial import; TOM complex