Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 25, 2020

Protein import by the mitochondrial disulfide relay in higher eukaryotes

  • Yannik Finger and Jan Riemer ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

The proteome of the mitochondrial intermembrane space (IMS) contains more than 100 proteins, all of which are synthesized on cytosolic ribosomes and consequently need to be imported by dedicated machineries. The mitochondrial disulfide relay is the major import machinery for soluble proteins in the IMS. Its major component, the oxidoreductase MIA40, interacts with incoming substrates, retains them in the IMS, and oxidatively folds them. After this reaction, MIA40 is reoxidized by the sulfhydryl oxidase augmenter of liver regeneration, which couples disulfide formation by this machinery to the activity of the respiratory chain. In this review, we will discuss the import of IMS proteins with a focus on recent findings showing the diversity of disulfide relay substrates, describing the cytosolic control of this import system and highlighting the physiological relevance of the disulfide relay machinery in higher eukaryotes.

Acknowledgments

The Deutsche Forschungsgemeinschaft, DFG (RI2150/5-1, RI2150/2-2, RTG2550/1, and CRC1218/TP B02) funds research in the Laboratory of J.R.

  1. Conflict of interest statement: None to declare.

References

Abe, Y., Shodai, T., Muto, T., Mihara, K., Torii, H., Nishikawa, S., Endo, T., and Kohda, D. (2000). Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100, 551–560.10.1016/S0092-8674(00)80691-1Search in Google Scholar

Allen, S., Balabanidou, V., Sideris, D.P., Lisowsky, T., and Tokatlidis, K. (2005). Erv1 mediates the MIA40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J. Mol. Biol. 353, 937–944.10.1016/j.jmb.2005.08.049Search in Google Scholar PubMed

Aras, S., Pak, O., Sommer, N., Finley, R., Huettemann, M., Weissmann, N., and Grossman, L.I. (2013). Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2. Nucleic Acids Res. 41, 2255–2266.10.1093/nar/gks1454Search in Google Scholar PubMed PubMed Central

Aras, S., Bai, M., Lee, I., Springett, R., Huettemann, M., and Grossman, L.I. (2015). MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism. Mitochondrion 20, 43–51.10.1016/j.mito.2014.10.003Search in Google Scholar PubMed

Arnesano, F., Balatri, E., Banci, L., Bertini, I., and Winge, D.R. (2005). Folding studies of Cox17 reveal an important interplay of cysteine oxidation and copper binding. Structure 13, 713–722.10.1016/j.str.2005.02.015Search in Google Scholar PubMed

Banci, L., Bertini, I., Cefaro, C., Ciofi-Baffoni, S., Gallo, A., Martinelli, M., Sideris, D.P., Katrakili, N., and Tokatlidis, K. (2009a). MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nat. Struct. Mol. Biol. 16, 198–206.10.1038/nsmb.1553Search in Google Scholar PubMed

Banci, L., Bertini, I., Ciofi-Baffoni, S., and Tokatlidis, K. (2009b). The coiled coil–helix–coiled coil–helix proteins may be redox proteins. FEBS Lett. 583, 1699–1702.10.1016/j.febslet.2009.03.061Search in Google Scholar PubMed

Banci, L., Bertini, I., Cefaro, C., Cenacchi, L., Ciofi-Baffoni, S., Felli, I.C., Gallo, A., Gonnelli, L., Luchinat, E., Sideris, D., et al. (2010). Molecular chaperone function of MIA40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import. Proc. Natl. Acad. Sci. USA 107, 20190–20195.10.1073/pnas.1010095107Search in Google Scholar PubMed PubMed Central

Banci, L., Bertini, I., Calderone, V., Cefaro, C., Ciofi-Baffoni, S., Gallo, A., Kallergi, E., Lionaki, E., Pozidis, C., and Tokatlidis, K. (2011). Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc. Natl. Acad. Sci. USA 108, 4811–4816.10.1073/pnas.1014542108Search in Google Scholar PubMed PubMed Central

Banci, L., Bertini, I., Calderone, V., Cefaro, C., Ciofi-Baffoni, S., Gallo, A., and Tokatlidis, K. (2012). An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J. Am. Chem. Soc. 134, 1442–1445.10.1021/ja209881fSearch in Google Scholar PubMed

Banci, L., Barbieri, L., Bertini, I., Luchinat, E., Secci, E., Zhao, Y., and Aricescu, A.R. (2013). Atomic-resolution monitoring of protein maturation in live human cells by NMR. Nat. Chem. Biol. 9, 297–299.10.1038/nchembio.1202Search in Google Scholar PubMed PubMed Central

Baughman, J.M., Nilsson, R., Gohil, V.M., Arlow, D.H., Gauhar, Z., and Mootha, V.K. (2009). A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genet. 5, e1000590.10.1371/journal.pgen.1000590Search in Google Scholar PubMed PubMed Central

Bien, M., Longen, S., Wagener, N., Chwalla, I., Herrmann, J.M., and Riemer, J. (2010). Mitochondrial disulfide bond formation is driven by intersubunit electron transfer in Erv1 and proofread by glutathione. Mol. Cell 37, 516–528.10.1016/j.molcel.2010.01.017Search in Google Scholar PubMed

Bihlmaier, K., Mesecke, N., Terziyska, N., Bien, M., Hell, K., and Herrmann, J.M. (2007). The disulfide relay system of mitochondria is connected to the respiratory chain. J. Cell Biol. 179, 389–395.10.1083/jcb.200707123Search in Google Scholar PubMed PubMed Central

Bottinger, L., Gornicka, A., Czerwik, T., Bragoszewski, P., Loniewska-Lwowska, A., Schulze-Specking, A., Truscott, K.N., Guiard, B., Milenkovic, D., and Chacinska, A. (2012). In vivo evidence for cooperation of MIA40 and Erv1 in the oxidation of mitochondrial proteins. Mol. Biol. Cell 23, 3957–3969.10.1091/mbc.e12-05-0358Search in Google Scholar PubMed PubMed Central

Bragoszewski, P., Gornicka, A., Sztolsztener, M.E., and Chacinska, A. (2013). The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins. Mol. Cell Biol. 33, 2136–2148.10.1128/MCB.01579-12Search in Google Scholar PubMed PubMed Central

Bragoszewski, P., Wasilewski, M., Sakowska, P., Gornicka, A.,Bottinger, L., Qiu, J., Wiedemann, N., and Chacinska, A. (2015). Retro-translocation of mitochondrial intermembrane space proteins. Proc. Natl. Acad. Sci. USA 112, 7713–7718.10.1073/pnas.1504615112Search in Google Scholar PubMed PubMed Central

Briston, T., Stephen, J.M., Thomas, L.W., Esposito, C., Chung, Y.L., Syafruddin, S.E., Turmaine, M., Maddalena, L.A., Greef, B., Szabadkai, G., et al. (2018). VHL-mediated regulation of CHCHD4 and mitochondrial function. Front. Oncol. 8, 388.10.3389/fonc.2018.00388Search in Google Scholar PubMed PubMed Central

Calderwood, L., Holm, I.A., Teot, L.A., and Anselm, I. (2016). Adrenal insufficiency in mitochondrial disease: a rare case of GFER-related mitochondrial encephalomyopathy and review of the literature. J. Child. Neurol. 31, 190–194.10.1177/0883073815587327Search in Google Scholar PubMed

Ceh-Pavia, E., Ang, S.K., Spiller, M.P., and Lu, H. (2014). The disease-associated mutation of the mitochondrial thiol oxidase Erv1 impairs cofactor binding during its catalytic reaction. Biochem. J. 464, 449–459.10.1042/BJ20140679Search in Google Scholar PubMed

Chacinska, A., Pfannschmidt, S., Wiedemann, N., Kozjak, V., Sanjuán Szklarz, L.K., Schulze-Specking, A., Truscott, K.N., Guiard, B., Meisinger, C., and Pfanner, N. (2004). Essential role of MIA40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J. 23, 3735–3746.10.1038/sj.emboj.7600389Search in Google Scholar PubMed PubMed Central

Chacinska, A., Guiard, B., Mueller, J.M., Schulze-Specking, A., Gabriel, K., Kutik, S., and Pfanner, N. (2008). Mitochondrial biogenesis, switching the sorting pathway of the intermembrane space receptor MIA40. J. Biol. Chem. 283, 29723–29729.10.1074/jbc.M805356200Search in Google Scholar PubMed PubMed Central

Daithankar, V.N., Farrell, S.R., and Thorpe, C. (2009). Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry 48, 4828–4837.10.1021/bi900347vSearch in Google Scholar PubMed PubMed Central

Daithankar, V.N., Schaefer, S.A., Dong, M., Bahnson, B.J., and Thorpe, C. (2010). Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry 49, 6737–6745.10.1021/bi100912mSearch in Google Scholar PubMed PubMed Central

Daithankar, V.N., Wang, W., Trujillo, J.R., and Thorpe, C. (2012). Flavin-linked Erv-family sulfhydryl oxidases release superoxide anion during catalytic turnover. Biochemistry 51, 265–272.10.1021/bi201672hSearch in Google Scholar PubMed PubMed Central

Darshi, M., Trinh, K.N., Murphy, A.N., and Taylor, S.S. (2012). Targeting and import mechanism of coiled-coil helix coiled-coil helix domain–containing protein 3 (ChChd3) into the mitochondrial intermembrane space. J. Biol. Chem. 287, 39480–39491.10.1074/jbc.M112.387696Search in Google Scholar PubMed PubMed Central

Denkert, N., Schendzielorz, A.B., Barbot, M., Versemann, L., Richter, F., Rehling, P., and Meinecke, M. (2017). Cation selectivity of the presequence translocase channel TIM23 is crucial for efficient protein import. eLife 6, pii: e28324.10.7554/eLife.28324Search in Google Scholar PubMed PubMed Central

Desai, N., Brown, A., Amunts, A., and Ramakrishnan, V. (2017). The structure of the yeast mitochondrial ribosome. Science 355, 528–531.10.1126/science.aal2415Search in Google Scholar PubMed PubMed Central

Di Fonzo, A., Ronchi, D., Lodi, T., Fassone, E., Tigano, M., Lamperti, C., Corti, S., Bordoni, A., Fortunato, F., Nizzardo, M., et al. (2009). The mitochondrial disulfide relay system protein GFER is mutated in autosomal–recessive myopathy with cataract and combined respiratory-chain deficiency. Am. J. Hum. Genet. 84, 594–604.10.1016/j.ajhg.2009.04.004Search in Google Scholar PubMed PubMed Central

Erdogan, A.J., Ali, M., Habich, M., Salscheider, S.L., Schu, L.,Petrungaro, C., Thomas, L.W., Ashcroft, M., Leichert, L.I., Roma, L.P., et al. (2018). The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo. Redox Biol. 17, 200–206.10.1016/j.redox.2018.03.014Search in Google Scholar PubMed PubMed Central

Farrell, S.R. and Thorpe, C. (2005). Augmenter of liver regeneration: a flavin-dependent sulfhydryl oxidase with cytochrome c reductase activity. Biochemistry 44, 1532–1541.10.1021/bi0479555Search in Google Scholar PubMed

Fetherolf, M.M., Boyd, S.D., Taylor, A.B., Kim, H.J., Wohlschlegel, J.A., Blackburn, N.J., Hart, P.J., Winge, D.R., and Winkler, D.D. (2017). Copper–zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. J. Biol. Chem. 292, 12025–12040.10.1074/jbc.M117.775981Search in Google Scholar PubMed PubMed Central

Field, L.S., Furukawa, Y., O’Halloran, T.V., and Culotta, V.C. (2003). Factors controlling the uptake of yeast copper/zinc superoxide dismutase into mitochondria. J. Biol. Chem. 278, 28052–28059.10.1074/jbc.M304296200Search in Google Scholar PubMed

Fischer, L.R., Igoudjil, A., Magrane, J., Li, Y., Hansen, J.M., Manfredi, G., and Glass, J.D. (2011). SOD1 targeted to the mitochondrial intermembrane space prevents motor neuropathy in the Sod1 knockout mouse. Brain 134, 196–209.10.1093/brain/awq314Search in Google Scholar PubMed PubMed Central

Fischer, M., Horn, S., Belkacemi, A., Kojer, K., Petrungaro, C., Habich, M., Ali, M., Kuettner, V., Bien, M., Kauff, F., et al. (2013). Protein import and oxidative folding in the mitochondrial intermembrane space of intact mammalian cells. Mol. Biol. Cell 24, 2160–2170.10.1091/mbc.e12-12-0862Search in Google Scholar PubMed PubMed Central

Friederich, M.W., Erdogan, A.J., Coughlin, C.R., Elos, M.T., Jiang, H., O’Rourke, C.P., Lovell, M.A., Wartchow, E., Gowan, K., Chatfield, K.C., et al. (2016). Mutations in the accessory subunit NDUFB10 result in isolated complex I deficiency and illustrate the critical role of intermembrane space import for complex I holoenzyme assembly. Hum. Mol. Genet. 26, ddw431.10.1093/hmg/ddw431Search in Google Scholar PubMed PubMed Central

Funayama, M., Ohe, K., Amo, T., Furuya, N., Yamaguchi, J., Saiki, S., Li, Y., Ogaki, K., Ando, M., Yoshino, H., et al. (2015). CHCHD2 mutations in autosomal dominant late-onset Parkinson’s disease: a genome-wide linkage and sequencing study. Lancet Neurol. 14, 274–282.10.1016/S1474-4422(14)70266-2Search in Google Scholar PubMed

Gandhi, C.R., Chaillet, J.R., Nalesnik, M.A., Kumar, S., Dangi, A., Demetris, A.J., Ferrell, R., Wu, T., Divanovic, S., Stankeiwicz, T., et al. (2015). Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice. Gastroenterology 148, 379–391 e374.10.1053/j.gastro.2014.10.008Search in Google Scholar PubMed PubMed Central

Gornicka, A., Bragoszewski, P., Chroscicki, P., Wenz, L.S., Schulz, C., Rehling, P., and Chacinska, A. (2014). A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria. Mol. Biol. Cell 25, 3999–4009.10.1091/mbc.e14-06-1155Search in Google Scholar

Gross, D.P., Burgard, C.A., Reddehase, S., Leitch, J.M., Culotta, V.C., and Hell, K. (2011). Mitochondrial Ccs1 contains a structural disulfide bond crucial for the import of this unconventional substrate by the disulfide relay system. Mol. Biol. Cell 22, 3758–3767.10.1091/mbc.e11-04-0296Search in Google Scholar

Grumbt, B., Stroobant, V., Terziyska, N., Israel, L., and Hell, K. (2007). Functional characterization of MIA40p, the central component of the disulfide relay system of the mitochondrial intermembrane space. J. Biol. Chem. 282, 37461–37470.10.1074/jbc.M707439200Search in Google Scholar PubMed

Guo, P.-C., Ma, J.-D., Jiang, Y.-L., Wang, S.-J., Bao, Z.-Z., Yu, X.-J., Chen, Y., and Zhou, C.-Z. (2012). Structure of yeast sulfhydryl oxidase erv1 reveals electron transfer of the disulfide relay system in the mitochondrial intermembrane space. J. Biol. Chem. 287, 34961–34969.10.1074/jbc.M112.394759Search in Google Scholar PubMed PubMed Central

Guo, R., Zong, S., Wu, M., Gu, J., and Yang, M. (2017). Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell 170, 1247–1257 e1212.10.1016/j.cell.2017.07.050Search in Google Scholar PubMed

Habich, M., Salscheider, S.L., Murschall, L.M., Hoehne, M.N., Fischer, M., Schorn, F., Petrungaro, C., Ali, M., Erdogan, A.J., Abou-Eid, S., et al. (2019a). Vectorial import via a metastable disulfide-linked complex allows for a quality control step and import by the mitochondrial disulfide relay. Cell Rep. 26, 759–774.e755.10.1016/j.celrep.2018.12.092Search in Google Scholar PubMed

Habich, M., Salscheider, S.L., and Riemer, J. (2019b). Cysteine residues in mitochondrial intermembrane space proteins: more than just import. Br. J. Pharmacol. 176, 514–531.10.1111/bph.14480Search in Google Scholar PubMed PubMed Central

Hangen, E., Feraud, O., Lachkar, S., Mou, H., Doti, N., Fimia, G.M., Lam, N.V., Zhu, C., Godin, I., Muller, K., et al. (2015). Interaction between AIF and CHCHD4 regulates respiratory chain biogenesis. Mol. Cell 58, 1001–1014.10.1016/j.molcel.2015.04.020Search in Google Scholar PubMed

Hawlitschek, G., Schneider, H., Schmidt, B., Tropschug, M., Hartl, F.U., and Neupert, W. (1988). Mitochondrial protein import: identification of processing peptidase and of PEP, a processing enhancing protein. Cell 53, 795–806.10.1016/0092-8674(88)90096-7Search in Google Scholar PubMed

Herrmann, J.M. and Kohl, R. (2007). Catch me if you can! Oxidative protein trapping in the intermembrane space of mitochondria. J. Cell Biol. 176, 559–563.10.1083/jcb.200611060Search in Google Scholar PubMed PubMed Central

Herrmann, J.M. and Riemer, J. (2010). The intermembrane space of mitochondria. Antioxid Redox Signal. 13, 1341–1358.10.1089/ars.2009.3063Search in Google Scholar PubMed

Herrmann, J.M. and Riemer, J. (2014). Three approaches to one problem: protein folding in the periplasm, the endoplasmic reticulum, and the intermembrane space. Antioxid Redox Signal. 21, 438–456.10.1089/ars.2014.5841Search in Google Scholar PubMed

Hill, K., Model, K., Ryan, M.T., Dietmeier, K., Martin, F., Wagner, R., and Pfanner, N. (1998). Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins. Nature 395, 516–521.10.1038/26780Search in Google Scholar PubMed

Hofmann, S., Rothbauer, U., Muehlenbein, N., Baiker, K., Hell, K., and Bauer, M.F. (2005). Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space. J. Mol. Biol. 353, 517–528.10.1016/j.jmb.2005.08.064Search in Google Scholar PubMed

Hudson, D.A. and Thorpe, C. (2015). MIA40 is a facile oxidant of unfolded reduced proteins but shows minimal isomerase activity. Arch. Biochem. Biophys. 579, 1–7.10.1016/j.abb.2015.05.005Search in Google Scholar PubMed PubMed Central

Hung, V., Zou, P., Rhee, H.-W., Udeshi, N.D., Cracan, V., Svinkina, T., Carr, S.A., Mootha, V.K., and Ting, A.Y. (2014). Proteomic mapping of the human mitochondrial intermembrane space in live cells via ratiometric APEX tagging. Mol. Cell 55, 332–341.10.1016/j.molcel.2014.06.003Search in Google Scholar PubMed PubMed Central

Ibrahim, S. and Weiss, T.S. (2019). Augmenter of liver regeneration: essential for growth and beyond. Cytokine Growth Factor Rev. 45, 65–80.10.1016/j.cytogfr.2018.12.003Search in Google Scholar PubMed

Igoudjil, A., Magrane, J., Fischer, L.R., Kim, H.J., Hervias, I., Dumont, M., Cortez, C., Glass, J.D., Starkov, A.A., and Manfredi, G. (2011). In vivo pathogenic role of mutant SOD1 localized in the mitochondrial intermembrane space. J. Neurosci. 31, 15826–15837.10.1523/JNEUROSCI.1965-11.2011Search in Google Scholar PubMed PubMed Central

Jin, C., Myers, A.M., and Tzagoloff, A. (1997). Cloning and characterization of MRP10, a yeast gene coding for a mitochondrial ribosomal protein. Curr. Genet. 31, 228–234.10.1007/s002940050199Search in Google Scholar PubMed

Kamer, K.J. and Mootha, V.K. (2014). MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. EMBO Rep. 15, 299–307.10.1002/embr.201337946Search in Google Scholar PubMed PubMed Central

Kawamata, H. and Manfredi, G. (2010). Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space. Antioxid Redox Signal. 13, 1375–1384.10.1089/ars.2010.3212Search in Google Scholar PubMed PubMed Central

Kawano, S., Yamano, K., Naoe, M., Momose, T., Terao, K., Nishikawa, S., Watanabe, N., and Endo, T. (2009). Structural basis of yeast TIM40/MIA40 as an oxidative translocator in the mitochondrial intermembrane space. Proc. Natl. Acad. Sci. USA 106, 14403–14407.10.1073/pnas.0901793106Search in Google Scholar PubMed PubMed Central

Kloppel, C., Michels, C., Zimmer, J., Herrmann, J.M., and Riemer, J. (2010). In yeast redistribution of Sod1 to the mitochondrial intermembrane space provides protection against respiration derived oxidative stress. Biochem. Biophys. Res. Commun. 403, 114–119.10.1016/j.bbrc.2010.10.129Search in Google Scholar PubMed

Kloppel, C., Suzuki, Y., Kojer, K., Petrungaro, C., Longen, S., Fiedler, S., Keller, S., and Riemer, J. (2011). MIA40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol. Mol. Biol. Cell 22, 3749–3757.10.1091/mbc.e11-04-0293Search in Google Scholar

Koc, E.C., Cimen, H., Kumcuoglu, B., Abu, N., Akpinar, G., Haque, M.E., Spremulli, L.L., and Koc, H. (2013). Identification and characterization of CHCHD1, AURKAIP1, and CRIF1 as new members of the mammalian mitochondrial ribosome. Front. Physiol. 4, 183.10.3389/fphys.2013.00183Search in Google Scholar PubMed PubMed Central

Koch, J.R. and Schmid, F.X. (2014a). MIA40 is optimized for function in mitochondrial oxidative protein folding and import. ACS Chem. Biol. 9, 2049–2057.10.1021/cb500408nSearch in Google Scholar PubMed

Koch, J.R. and Schmid, F.X. (2014b). MIA40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria. Nat. Commun. 5, 3041.10.1038/ncomms4041Search in Google Scholar PubMed

Kojer, K., Bien, M., Gangel, H., Morgan, B., Dick, T.P., and Riemer, J. (2012). Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the MIA40 redox state. EMBO J. 31, 3169–3182.10.1038/emboj.2012.165Search in Google Scholar PubMed PubMed Central

Kowalski, L., Bragoszewski, P., Khmelinskii, A., Glow, E., Knop, M., and Chacinska, A. (2018). Determinants of the cytosolic turnover of mitochondrial intermembrane space proteins. BMC Biol. 16, 66.10.1186/s12915-018-0536-1Search in Google Scholar PubMed PubMed Central

Kozakov, D., Hall, D.R., Xia, B., Porter, K.A., Padhorny, D., Yueh, C., Beglov, D., and Vajda, S. (2017). The ClusPro web server for protein–protein docking. Nat. Protoc. 12, 255–278.10.1038/nprot.2016.169Search in Google Scholar PubMed PubMed Central

Lamb, A.L., Wernimont, A.K., Pufahl, R.A., O’Halloran, T.V., and Rosenzweig, A.C. (2000). Crystal structure of the second domain of the human copper chaperone for superoxide dismutase. Biochemistry 39, 1589–1595.10.1021/bi992822iSearch in Google Scholar PubMed

Li, Y., Farooq, M., Sheng, D., Chandramouli, C., Lan, T., Mahajan, N.K., Kini, R.M., Hong, Y., Lisowsky, T., and Ge, R. (2012). Augmenter of liver regeneration (ALR) promotes liver outgrowth during zebrafish hepatogenesis. PLoS One 7, e30835.10.1371/journal.pone.0030835Search in Google Scholar PubMed PubMed Central

Liu, H., Li, Y., Li, Y., Liu, B., Wu, H., Wang, J., Wang, Y., Wang, M., Tang, S.-C., Zhou, Q., et al. (2012). Cloning and functional analysis of FLJ20420: a novel transcription factor for the BAG-1 promoter. PLoS One 7, e34832.10.1371/journal.pone.0034832Search in Google Scholar PubMed PubMed Central

Liu, Y., Clegg, H.V., Leslie, P.L., Di, J., Tollini, L.A., He, Y., Kim, T.-H., Jin, A., Graves, L.M., Zheng, J., et al. (2015). CHCHD2 inhibits apoptosis by interacting with Bcl-x L to regulate Bax activation. Cell Death Differ. 22, 1035–1046.10.1038/cdd.2014.194Search in Google Scholar PubMed PubMed Central

Longen, S., Woellhaf, M.W., Petrungaro, C., Riemer, J., and Herrmann, J.M. (2014). The disulfide relay of the intermembrane space oxidizes the ribosomal subunit Mrp10 on its transit into the mitochondrial matrix. Dev. Cell 28, 30–42.10.1016/j.devcel.2013.11.007Search in Google Scholar PubMed

Mesecke, N., Terziyska, N., Kozany, C., Baumann, F., Neupert, W., Hell, K., and Herrmann, J.M. (2005). A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell 121, 1059–1069.10.1016/j.cell.2005.04.011Search in Google Scholar PubMed

Meyer, K., Buettner, S., Ghezzi, D., Zeviani, M., Bano, D., and Nicotera, P. (2015). Loss of apoptosis-inducing factor critically affects MIA40 function. Cell Death Dis. 6, e1814.10.1038/cddis.2015.170Search in Google Scholar PubMed PubMed Central

Milenkovic, D., Ramming, T., Muller, J.M., Wenz, L.S., Gebert, N., Schulze-Specking, A., Stojanovski, D., Rospert, S., and Chacinska, A. (2009). Identification of the signal directing TIM9 and TIM10 into the intermembrane space of mitochondria. Mol. Biol. Cell 20, 2530–2539.10.1091/mbc.e08-11-1108Search in Google Scholar PubMed PubMed Central

Mohanraj, K., Wasilewski, M., Beninca, C., Cysewski, D., Poznanski, J., Sakowska, P., Bugajska, Z., Deckers, M., Dennerlein, S., Fernandez-Vizarra, E., et al. (2019). Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7. EMBO Mol Med. 11, pii: e9561.10.15252/emmm.201809561Search in Google Scholar PubMed PubMed Central

Mossmann, D., Meisinger, C., and Vogtle, F.N. (2012). Processing of mitochondrial presequences. Biochim Biophys Acta 1819, 1098–1106.10.1016/j.bbagrm.2011.11.007Search in Google Scholar PubMed

Nambot, S., Gavrilov, D., Thevenon, J., Bruel, A.L., Bainbridge, M., Rio, M., Goizet, C., Rotig, A., Jaeken, J., Niu, N., et al. (2017). Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data. Clin. Genet. 92, 188–198.10.1111/cge.12985Search in Google Scholar PubMed

Naoe, M., Ohwa, Y., Ishikawa, D., Ohshima, C., Nishikawa, S., Yamamoto, H., and Endo, T. (2004). Identification of TIM40 that mediates protein sorting to the mitochondrial intermembrane space. J. Biol. Chem. 279, 47815–47821.10.1074/jbc.M410272200Search in Google Scholar PubMed

Neal, S.E., Dabir, D.V., Wijaya, J., Boon, C., and Koehler, C.M. (2017). Osm1 facilitates the transfer of electrons from Erv1 to fumarate in the redox-regulated import pathway in the mitochondrial intermembrane space. Mol. Biol. Cell 28, 2773–2785.10.1091/mbc.e16-10-0712Search in Google Scholar PubMed PubMed Central

Park, J.-S., Davis, R.L., and Sue, C.M. (2018). Mitochondrial dysfunction in Parkinson’s disease: new mechanistic insights and therapeutic perspectives. Curr. Neurol. Neurosci. Rep. 18, 21.10.1007/s11910-018-0829-3Search in Google Scholar PubMed PubMed Central

Patron, M., Checchetto, V., Raffaello, A., Teardo, E., Vecellio Reane, D., Mantoan, M., Granatiero, V., Szabo, I., De Stefani, D., and Rizzuto, R. (2014). MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol. Cell 53, 726–737.10.1016/j.molcel.2014.01.013Search in Google Scholar PubMed PubMed Central

Peleh, V., Cordat, E., and Herrmann, J.M. (2016). Mia40 is a trans-site receptor that drives protein import into the mitochondrial intermembrane space by hydrophobic substrate binding. eLife 5, pii: e16177.10.7554/eLife.16177.014Search in Google Scholar

Petrungaro, C. and Riemer, J. (2014). Mechanisms and physiological impact of the dual localization of mitochondrial intermembrane space proteins. Biochem. Soc. Trans. 42, 952–958.10.1042/BST20140104Search in Google Scholar PubMed

Petrungaro, C., Zimmermann, K.M., Kuettner, V., Fischer, M., Dengjel, J.R., Bogeski, I., and Riemer, J. (2015). The Ca2+-dependent release of the MIA40-induced MICU1–MICU2 dimer from MCU regulates mitochondrial Ca2+ uptake. Cell Metab. 22, 721–733.10.1016/j.cmet.2015.08.019Search in Google Scholar PubMed

Ramesh, A., Peleh, V., Martinez-Caballero, S., Wollweber, F., Sommer, F., van der Laan, M., Schroda, M., Alexander, R.T., Campo, M.L., and Herrmann, J.M. (2016). A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J. Cell Biol. 214, 417–431.10.1083/jcb.201602074Search in Google Scholar PubMed PubMed Central

Reddehase, S., Grumbt, B., Neupert, W., and Hell, K. (2009). The disulfide relay system of mitochondria is required for the biogenesis of mitochondrial Ccs1 and Sod1. J. Mol. Biol. 385, 331–338.10.1016/j.jmb.2008.10.088Search in Google Scholar PubMed

Rissler, M., Wiedemann, N., Pfannschmidt, S., Gabriel, K., Guiard, B., Pfanner, N., and Chacinska, A. (2005). The essential mitochondrial protein Erv1 cooperates with MIA40 in biogenesis of intermembrane space proteins. J. Mol. Biol. 353, 485–492.10.1016/j.jmb.2005.08.051Search in Google Scholar PubMed

Roise, D., Horvath, S.J., Tomich, J.M., Richards, J.H., and Schatz, G. (1986). A chemically synthesized pre-sequence of an imported mitochondrial protein can form an amphiphilic helix and perturb natural and artificial phospholipid bilayers. EMBO J. 5, 1327–1334.10.1002/j.1460-2075.1986.tb04363.xSearch in Google Scholar PubMed PubMed Central

Sakowska, P., Jans, D.C., Mohanraj, K., Riedel, D., Jakobs, S., and Chacinska, A. (2015). The oxidation status of Mic19 regulates MICOS assembly. Mol. Cell. Biol. 35, 4222–4237.10.1128/MCB.00578-15Search in Google Scholar PubMed PubMed Central

Schaefer-Ramadan, S., Gannon, S.A., and Thorpe, C. (2013). Human augmenter of liver regeneration: probing the catalytic mechanism of a flavin-dependent sulfhydryl oxidase. Biochemistry 52, 8323–8332.10.1021/bi401305wSearch in Google Scholar PubMed PubMed Central

Sideris, D.P., Petrakis, N., Katrakili, N., Mikropoulou, D., Gallo, A., Ciofi-Baffoni, S., Banci, L., Bertini, I., and Tokatlidis, K. (2009). A novel intermembrane space-targeting signal docks cysteines onto MIA40 during mitochondrial oxidative folding. J. Cell Biol. 187, 1007–1022.10.1083/jcb.200905134Search in Google Scholar PubMed PubMed Central

Sokol, A.M., Uszczynska-Ratajczak, B., Collins, M.M., Bazala, M., Topf, U., Lundegaard, P.R., Sugunan, S., Guenther, S., Kuenne, C., Graumann, J., et al. (2018). Loss of the MIA40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish. PLoS Genet. 14, e1007743.10.1371/journal.pgen.1007743Search in Google Scholar PubMed PubMed Central

Sturtz, L.A., Diekert, K., Jensen, L.T., Lill, R., and Culotta, V.C. (2001). A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J. Biol. Chem. 276, 38084–38089.10.1074/jbc.M105296200Search in Google Scholar PubMed

Sun, Y., Li, T., Xie, C., Xu, Y., Zhou, K., Rodriguez, J., Han, W., Wang, X., Kroemer, G., Modjtahedi, N., et al. (2017). Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia–ischemia. Cell Death Dis. 8, e2781.10.1038/cddis.2017.196Search in Google Scholar PubMed PubMed Central

Suzuki, Y., Ali, M., Fischer, M., and Riemer, J. (2013). Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria. Nat. Commun. 4, 2430.10.1038/ncomms3430Search in Google Scholar PubMed

Sztolsztener, M.E., Brewinska, A., Guiard, B., and Chacinska, A. (2013). Disulfide bond formation: sulfhydryl oxidase ALR Controls mitochondrial biogenesis of human MIA40. Traffic 14, 309–320.10.1111/tra.12030Search in Google Scholar PubMed

Terziyska, N., Lutz, T., Kozany, C., Mokranjac, D., Mesecke, N., Neupert, W., Herrmann, J.M., and Hell, K. (2005). MIA40, a novel factor for protein import into the intermembrane space of mitochondria is able to bind metal ions. FEBS Lett. 579, 179–184.10.1016/j.febslet.2004.11.072Search in Google Scholar PubMed

Terziyska, N., Grumbt, B., Kozany, C., and Hell, K. (2009). Structural and functional roles of the conserved cysteine residues of the redox-regulated import receptor Mia40 in the intermembrane space of mitochondria. J. Biol. Chem. 284, 1353–1363.10.1074/jbc.M805035200Search in Google Scholar PubMed

Thinon, E., Serwa, R.A., Broncel, M., Brannigan, J.A., Brassat, U., Wright, M.H., Heal, W.P., Wilkinson, A.J., Mann, D.J., and Tate, E.W. (2014). Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat. Commun. 5, 4919.10.1038/ncomms5919Search in Google Scholar PubMed PubMed Central

Thomas, L.W., Staples, O., Turmaine, M., and Ashcroft, M. (2017). CHCHD4 regulates intracellular oxygenation and perinuclear distribution of mitochondria. Front Oncol. 7, 71.10.3389/fonc.2017.00071Search in Google Scholar PubMed PubMed Central

Thomas, L.W., Esposito, C., Stephen, J.M., Costa, A.S.H., Frezza, C., Blacker, T.S., Szabadkai, G., and Ashcroft, M. (2019). CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain–mediated metabolism. Cancer Metab. 7, 7.10.1186/s40170-019-0200-4Search in Google Scholar PubMed PubMed Central

Timmis, J.N., Ayliffe, M.A., Huang, C.Y., and Martin, W. (2004).Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat. Rev. Genet. 5, 123–135.10.1038/nrg1271Search in Google Scholar PubMed

Ueda, E., Tamura, Y., Sakaue, H., Kawano, S., Kakuta, C., Matsumoto, S., and Endo, T. (2019). Myristoyl group–aided protein import into the mitochondrial intermembrane space. Sci. Rep. 9, 1185.10.1038/s41598-018-38016-1Search in Google Scholar PubMed PubMed Central

van Zundert, G.C.P., Rodrigues, J.P.G.L.M., Trellet, M., Schmitz, C., Kastritis, P.L., Karaca, E., Melquiond, A.S.J., van Dijk, M., de Vries, S.J., and Bonvin, A.M.J.J. (2016). The HADDOCK2.2 web server: user-friendly integrative modeling of biomolecular complexes. J. Mol. Biol. 428, 720–725.10.1016/j.jmb.2015.09.014Search in Google Scholar PubMed

Vogtle, F.N., Burkhart, J.M., Rao, S., Gerbeth, C., Hinrichs, J., Martinou, J.C., Chacinska, A., Sickmann, A., Zahedi, R.P., and Meisinger, C. (2012). Intermembrane space proteome of yeast mitochondria. Mol Cell Proteomics 11, 1840–1852.10.1074/mcp.M112.021105Search in Google Scholar PubMed PubMed Central

von der Malsburg, K., Muller, J.M., Bohnert, M., Oeljeklaus, S., Kwiatkowska, P., Becker, T., Loniewska-Lwowska, A., Wiese, S., Rao, S., Milenkovic, D., et al. (2011). Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis. Dev Cell. 21, 694–707.10.1016/j.devcel.2011.08.026Search in Google Scholar PubMed

Weckbecker, D., Longen, S., Riemer, J., and Herrmann, J.M. (2012). Atp23 biogenesis reveals a chaperone-like folding activity of MIA40 in the IMS of mitochondria. EMBO J. 31, 4348–4358.10.1038/emboj.2012.263Search in Google Scholar PubMed PubMed Central

Wiedemann, N. and Pfanner, N. (2017). Mitochondrial machineries for protein import and assembly. Annu. Rev. Biochem. 86, 685–714.10.1146/annurev-biochem-060815-014352Search in Google Scholar PubMed

Wrobel, L., Trojanowska, A., Sztolsztener, M.E., and Chacinska, A. (2013). Mitochondrial protein import: MIA40 facilitates TIM22 translocation into the inner membrane of mitochondria. Mol. Biol. Cell. 24, 543–554.10.1091/mbc.e12-09-0649Search in Google Scholar

Wrobel, L., Topf, U., Bragoszewski, P., Wiese, S., Sztolsztener, M.E., Oeljeklaus, S., Varabyova, A., Lirski, M., Chroscicki, P., Mroczek, S., et al. (2015). Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature 524, 485–488.10.1038/nature14951Search in Google Scholar PubMed

Wrobel, L., Sokol, A.M., Chojnacka, M., and Chacinska, A. (2016). The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly. Sci. Rep. 6, 27484.10.1038/srep27484Search in Google Scholar PubMed PubMed Central

Wu, C.-K., Dailey, T.A., Dailey, H.A., Wang, B.-C., and Rose, J.P. (2003). The crystal structure of augmenter of liver regeneration: a mammalian FAD-dependent sulfhydryl oxidase. Protein Sci. 12, 1109–1118.10.1110/ps.0238103Search in Google Scholar PubMed PubMed Central

Xia, B., Vajda, S., and Kozakov, D. (2016). Accounting for pairwise distance restraints in FFT-based protein–protein docking. Bioinformatics 32, 3342–3344.10.1093/bioinformatics/btw306Search in Google Scholar PubMed PubMed Central

Yang, J., Staples, O., Thomas, L.W., Briston, T., Robson, M., Poon, E., Simoes, M.L., El-Emir, E., Buffa, F.M., Ahmed, A., et al. (2012). Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression. J. Clin. Invest. 122, 600–611.10.1172/JCI58780Search in Google Scholar PubMed PubMed Central

Zhu, J., Vinothkumar, K.R., and Hirst, J. (2016). Structure of mammalian respiratory complex I. Nature 536, 354–358.10.1038/nature19095Search in Google Scholar PubMed PubMed Central

Received: 2020-01-07
Accepted: 2020-02-24
Published Online: 2020-03-25
Published in Print: 2020-05-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1515/hsz-2020-0108/html
Scroll to top button