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Transport of Proteins into Mitochondria

  • Katja G. Hansen
  • Johannes M. HerrmannEmail author
Article
  • 143 Downloads

Abstract

Mitochondria are essential organelles of eukaryotic cells. They consist of hundreds of different proteins that exhibit crucial activities in respiration, catabolic metabolism and the synthesis of amino acids, lipids, heme and iron-sulfur clusters. With the exception of a handful of hydrophobic mitochondrially encoded membrane proteins, all these proteins are synthesized on cytosolic ribosomes, targeted to receptors on the mitochondrial surface, and transported across or inserted into the outer and inner mitochondrial membrane before they are folded and assembled into their final native structure. This review article provides a comprehensive overview of the mechanisms and components of the mitochondrial protein import systems with a particular focus on recent developments in the field.

Keywords

ER-SURF Mitochondria Protein import Targeting signals 

Notes

Acknowledgements

We thank Janina Laborenz and Clara Stiefel for critical reading of the manuscript. This work was funded by grants of the Deutsche Forschungsgemeinschaft (He2803/4-2, SPP1710 and IRTG1830 and DIP Mitobalance).

Compliance with Ethical Standards

Conflict of interest

The authors KGH and JMH declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Blobel G (1980) Intracellular protein topogenesis. Proc Natl Acad Sci USA 77(3):1496–1500CrossRefPubMedGoogle Scholar
  2. 2.
    Vögtle F-N, Burkhart JM, Gonczarowska-Jorge H et al (2017) Landscape of submitochondrial protein distribution. Nat Commun 8(1):290.  https://doi.org/10.1038/s41467-017-00359-0 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Paumard P, Vaillier J, Coulary B et al (2002) The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J 21(3):221–230.  https://doi.org/10.1093/emboj/21.3.221 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pfeffer S, Woellhaf MW, Herrmann JM et al (2015) Organization of the mitochondrial translation machinery studied in situ by cryoelectron tomography. Nat Commun 6:6019.  https://doi.org/10.1038/ncomms7019 CrossRefPubMedGoogle Scholar
  5. 5.
    Hessenberger M, Zerbes RM, Rampelt H et al (2017) Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions. Nat Commun 8:15258.  https://doi.org/10.1038/ncomms15258 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Tarasenko D, Barbot M, Jans DC et al (2017) The MICOS component Mic60 displays a conserved membrane-bending activity that is necessary for normal cristae morphology. J Cell Biol 216(4):889–899.  https://doi.org/10.1083/jcb.201609046 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rampelt H, van der Laan M (2017) The Yin & Yang of mitochondrial architecture—interplay of MICOS and F1Fo-ATP synthase in cristae formation. Microb Cell 4(8):236–239.  https://doi.org/10.15698/mic2017.08.583 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Eydt K, Davies KM, Behrendt C et al (2017) Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10. Microb Cell 4(8):259–272.  https://doi.org/10.15698/mic2017.08.585 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Harner ME, Unger A-K, Izawa T et al (2014) Aim24 and MICOS modulate respiratory function, tafazzin-related cardiolipin modification and mitochondrial architecture. Elife 3:e01684.  https://doi.org/10.7554/eLife.01684 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kawano S, Tamura Y, Kojima R et al (2018) Structure-function insights into direct lipid transfer between membranes by Mmm1-Mdm12 of ERMES. J Cell Biol 217(3):959–974.  https://doi.org/10.1083/jcb.201704119 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Herrmann JM, Riemer J (2010) The intermembrane space of mitochondria. Antioxid Redox Signal 13(9):1341–1358.  https://doi.org/10.1089/ars.2009.3063 CrossRefPubMedGoogle Scholar
  12. 12.
    Möller-Hergt BV, Carlström A, Stephan K et al (2018) The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria. Mol Biol Cell 29(20):2386–2396.  https://doi.org/10.1091/mbc.E18-04-0227 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kummer E, Leibundgut M, Rackham O et al (2018) Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM. Nature 560(7717):263–267.  https://doi.org/10.1038/s41586-018-0373-y CrossRefPubMedGoogle Scholar
  14. 14.
    Morgenstern M, Stiller SB, Lübbert P et al (2017) Definition of a high-confidence mitochondrial proteome at quantitative scale. Cell Rep 19(13):2836–2852.  https://doi.org/10.1016/j.celrep.2017.06.014 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Calvo SE, Clauser KR, Mootha VK (2016) MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins. Nucleic Acids Res 44(D1):D1251–D1257.  https://doi.org/10.1093/nar/gkv1003 CrossRefPubMedGoogle Scholar
  16. 16.
    Wrobel L, Topf U, Bragoszewski P et al (2015) Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature 524(7566):485–488.  https://doi.org/10.1038/nature14951 CrossRefPubMedGoogle Scholar
  17. 17.
    Weidberg H, Amon A (2018) MitoCPR-A surveillance pathway that protects mitochondria in response to protein import stress. Science 360(6385).  https://doi.org/10.1126/science.aan4146
  18. 18.
    Wang X, Chen XJ (2015) A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death. Nature 524(7566):481–484.  https://doi.org/10.1038/nature14859 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Labbadia J, Brielmann RM, Neto MF et al (2017) Mitochondrial stress restores the heat shock response and prevents proteostasis collapse during aging. Cell Rep 21(6):1481–1494.  https://doi.org/10.1016/j.celrep.2017.10.038 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fiorese CJ, Schulz AM, Lin Y-F et al (2016) The transcription factor ATF5 mediates a mammalian mitochondrial UPR. Curr Biol 26(15):2037–2043.  https://doi.org/10.1016/j.cub.2016.06.002 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Gruber A, Hornburg D, Antonin M et al (2018) Molecular and structural architecture of polyQ aggregates in yeast. Proc Natl Acad Sci USA 115(15):E3446–E3453.  https://doi.org/10.1073/pnas.1717978115 CrossRefPubMedGoogle Scholar
  22. 22.
    Liu W, Duan X, Fang X et al (2018) Mitochondrial protein import regulates cytosolic protein homeostasis and neuronal integrity. Autophagy 14(8):1293–1309.  https://doi.org/10.1080/15548627.2018.1474991 CrossRefPubMedGoogle Scholar
  23. 23.
    Papsdorf K, Kaiser CJO, Drazic A et al (2015) Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects. BMC Genom 16:662.  https://doi.org/10.1186/s12864-015-1831-7 CrossRefGoogle Scholar
  24. 24.
    Aviram N, Schuldiner M (2017) Targeting and translocation of proteins to the endoplasmic reticulum at a glance. J Cell Sci 130(24):4079–4085.  https://doi.org/10.1242/jcs.204396 CrossRefPubMedGoogle Scholar
  25. 25.
    Young JC, Hoogenraad NJ, Hartl FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112(1):41–50.  https://doi.org/10.1016/S0092-8674(02)01250-3 CrossRefPubMedGoogle Scholar
  26. 26.
    Cichocki BA, Krumpe K, Vitali DG et al (2018) Pex19 is involved in importing dually targeted tail-anchored proteins to both mitochondria and peroxisomes. Traffic.  https://doi.org/10.1111/tra.12604 CrossRefPubMedGoogle Scholar
  27. 27.
    Jores T, Lawatscheck J, Beke V et al (2018) Cytosolic Hsp70 and Hsp40 chaperones enable the biogenesis of mitochondrial β-barrel proteins. J Cell Biol.  https://doi.org/10.1083/jcb.201712029 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Vögtle F-N, Wortelkamp S, Zahedi RP et al (2009) Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139(2):428–439.  https://doi.org/10.1016/j.cell.2009.07.045 CrossRefPubMedGoogle Scholar
  29. 29.
    Sinzel M, Tan T, Wendling P et al (2016) Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP-dependent biogenesis pathway. EMBO Rep 17(7):965–981.  https://doi.org/10.15252/embr.201541273 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Doyle SR, Kasinadhuni NRP, Chan CK et al (2013) Evidence of evolutionary constraints that influences the sequence composition and diversity of mitochondrial matrix targeting signals. PLoS ONE 8(6):e67938.  https://doi.org/10.1371/journal.pone.0067938 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Geissler A, Krimmer T, Bömer U et al (2000) Membrane potential-driven protein import into mitochondria. The sorting sequence of cytochrome b(2) modulates the deltapsi-dependence of translocation of the matrix-targeting sequence. Mol Biol Cell 11(11):3977–3991.  https://doi.org/10.1091/mbc.11.11.3977 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Huang S, Taylor NL, Whelan J et al (2009) Refining the definition of plant mitochondrial presequences through analysis of sorting signals, N-terminal modifications, and cleavage Motifs1WOA. Plant Physiol 150(3):1272–1285.  https://doi.org/10.1104/pp.109.137885 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Backes S, Hess S, Boos F et al (2018) Tom70 enhances mitochondrial preprotein import efficiency by binding to internal targeting sequences. J Cell Biol 217(4):1369–1382.  https://doi.org/10.1083/jcb.201708044 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Boos F, Mühlhaus T, Herrmann J (2018) Detection of internal matrix targeting signal-like sequences (iMTS-Ls) in mitochondrial precursor proteins using the TargetP prediction tool. Biol Protoc.  https://doi.org/10.21769/BioProtoc.2474 CrossRefGoogle Scholar
  35. 35.
    Wiedemann N, Pfanner N, Ryan MT (2001) The three modules of ADP/ATP carrier cooperate in receptor recruitment and translocation into mitochondria. EMBO J 20(5):951–960.  https://doi.org/10.1093/emboj/20.5.951 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Fölsch H, Guiard B, Neupert W et al (1996) Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria. EMBO J 15(3):479–487CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ma Y, Taylor SS (2008) A molecular switch for targeting between endoplasmic reticulum (ER) and mitochondria: conversion of a mitochondria-targeting element into an ER-targeting signal in DAKAP1. J Biol Chem 283(17):11743–11751.  https://doi.org/10.1074/jbc.M710494200 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Costello JL, Castro IG, Camões F et al (2017) Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells. J Cell Sci 130(9):1675–1687.  https://doi.org/10.1242/jcs.200204 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Kemper C, Habib SJ, Engl G et al (2008) Integration of tail-anchored proteins into the mitochondrial outer membrane does not require any known import components. J Cell Sci 121(Pt 12):1990–1998.  https://doi.org/10.1242/jcs.024034 CrossRefPubMedGoogle Scholar
  40. 40.
    Marty NJ, Teresinski HJ, Hwang YT et al (2014) New insights into the targeting of a subset of tail-anchored proteins to the outer mitochondrial membrane. Front Plant Sci 5:426.  https://doi.org/10.3389/fpls.2014.00426 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Krumpe K, Frumkin I, Herzig Y et al (2012) Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes. Mol Biol Cell 23(20):3927–3935.  https://doi.org/10.1091/mbc.E11-12-0994 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Chen Y-C, Umanah GKE, Dephoure N et al (2014) Msp1/ATAD1 maintains mitochondrial function by facilitating the degradation of mislocalized tail-anchored proteins. EMBO J 33(14):1548–1564.  https://doi.org/10.15252/embj.201487943 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Okreglak V, Walter P (2014) The conserved AAA-ATPase Msp1 confers organelle specificity to tail-anchored proteins. Proc Natl Acad Sci USA 111(22):8019–8024.  https://doi.org/10.1073/pnas.1405755111 CrossRefPubMedGoogle Scholar
  44. 44.
    Ahting U, Waizenegger T, Neupert W et al (2005) Signal-anchored proteins follow a unique insertion pathway into the outer membrane of mitochondria. J Biol Chem 280(1):48–53.  https://doi.org/10.1074/jbc.M410905200 CrossRefPubMedGoogle Scholar
  45. 45.
    Jores T, Klinger A, Groß LE et al (2016) Characterization of the targeting signal in mitochondrial β-barrel proteins. Nat Commun 7:12036.  https://doi.org/10.1038/ncomms12036 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gratzer S (1995) Mas37p, a novel receptor subunit for protein import into mitochondria. J Cell Biol 129(1):25–34.  https://doi.org/10.1083/jcb.129.1.25 CrossRefPubMedGoogle Scholar
  47. 47.
    Imai K, Fujita N, Gromiha MM et al (2011) Eukaryote-wide sequence analysis of mitochondrial β-barrel outer membrane proteins. BMC Genom 12:79.  https://doi.org/10.1186/1471-2164-12-79 CrossRefGoogle Scholar
  48. 48.
    Sideris DP, Petrakis N, Katrakili N et al (2009) A novel intermembrane space-targeting signal docks cysteines onto Mia40 during mitochondrial oxidative folding. J Cell Biol 187(7):1007–1022.  https://doi.org/10.1083/jcb.200905134 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Milenkovic D, Ramming T, Müller JM et al (2009) Identification of the signal directing Tim9 and Tim10 into the intermembrane space of mitochondria. Mol Biol Cell 20(10):2530–2539.  https://doi.org/10.1091/mbc.E08-11-1108 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Longen S, Bien M, Bihlmaier K et al (2009) Systematic analysis of the twin cx(9)c protein family. J Mol Biol 393(2):356–368.  https://doi.org/10.1016/j.jmb.2009.08.041 CrossRefPubMedGoogle Scholar
  51. 51.
    Gabriel K, Milenkovic D, Chacinska A et al (2007) Novel mitochondrial intermembrane space proteins as substrates of the MIA import pathway. J Mol Biol 365(3):612–620.  https://doi.org/10.1016/j.jmb.2006.10.038 CrossRefPubMedGoogle Scholar
  52. 52.
    Vögtle F-N, Burkhart JM, Rao S et al (2012) Intermembrane space proteome of yeast mitochondria. Mol Cell Proteom 11(12):1840–1852.  https://doi.org/10.1074/mcp.M112.021105 CrossRefGoogle Scholar
  53. 53.
    Peleh V, Zannini F, Backes S et al (2017) Erv1 of Arabidopsis thaliana can directly oxidize mitochondrial intermembrane space proteins in the absence of redox-active Mia40. BMC Biol 15(1):106.  https://doi.org/10.1186/s12915-017-0445-8 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Peleh V, Cordat E, Herrmann JM (2016) Mia40 is a trans-site receptor that drives protein import into the mitochondrial intermembrane space by hydrophobic substrate binding. Elife 5:e16177.  https://doi.org/10.7554/eLife.16177 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Emanuelsson O, Nielsen H, Brunak S et al (2000) Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol 300(4):1005–1016.  https://doi.org/10.1006/jmbi.2000.3903 CrossRefPubMedGoogle Scholar
  56. 56.
    Claros MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241(3):779–786CrossRefPubMedGoogle Scholar
  57. 57.
    Ohlmeier S, Kastaniotis AJ, Hiltunen JK et al (2004) The yeast mitochondrial proteome, a study of fermentative and respiratory growth. J Biol Chem 279(6):3956–3979.  https://doi.org/10.1074/jbc.M310160200 CrossRefPubMedGoogle Scholar
  58. 58.
    Hung V, Zou P, Rhee H-W et al (2014) Proteomic mapping of the human mitochondrial intermembrane space in live cells via ratiometric APEX tagging. Mol Cell 55(2):332–341.  https://doi.org/10.1016/j.molcel.2014.06.003 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Hung V, Lam SS, Udeshi ND et al (2017) Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in living human cells by proximity biotinylation. Elife 6:e24463.  https://doi.org/10.7554/eLife.24463 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Caplan AJ, Cyr DM, Douglas MG (1992) YDJ1p facilitates polypeptide translocation across different intracellular membranes by a conserved mechanism. Cell 71(7):1143–1155CrossRefPubMedGoogle Scholar
  61. 61.
    Deshaies RJ, Koch BD, Werner-Washburne M et al (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332(6167):800–805.  https://doi.org/10.1038/332800a0 CrossRefPubMedGoogle Scholar
  62. 62.
    Lee DH, Sherman MY, Goldberg AL (1996) Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent degradation of short-lived and abnormal proteins in Saccharomyces cerevisiae. Mol Cell Biol 16(9):4773–4781CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Sahi C, Kominek J, Ziegelhoffer T et al (2013) Sequential duplications of an ancient member of the DnaJ-family expanded the functional chaperone network in the eukaryotic cytosol. Mol Biol Evol 30(5):985–998.  https://doi.org/10.1093/molbev/mst008 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Opaliński Ł, Song J, Priesnitz C et al (2018) Recruitment of cytosolic J-proteins by TOM receptors promotes mitochondrial protein biogenesis. Cell Rep 25(8):2036–2043.e5.  https://doi.org/10.1016/j.celrep.2018.10.083 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hoseini H, Pandey S, Jores T et al (2016) The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology. FEBS J 283(18):3338–3352.  https://doi.org/10.1111/febs.13813 CrossRefPubMedGoogle Scholar
  66. 66.
    Itakura E, Zavodszky E, Shao S et al (2016) Ubiquilins chaperone and triage mitochondrial membrane proteins for degradation. Mol Cell 63(1):21–33.  https://doi.org/10.1016/j.molcel.2016.05.020 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Gold VAM, Chroscicki P, Bragoszewski P et al (2017) Visualization of cytosolic ribosomes on the surface of mitochondria by elect ron cryo-tomography. EMBO Rep 18(10):1786–1800.  https://doi.org/10.15252/embr.201744261 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Wienhues U, Becker K, Schleyer M et al (1991) Protein folding causes an arrest of preprotein translocation into mitochondria in vivo. J Cell Biol 115(6):1601–1609CrossRefPubMedGoogle Scholar
  69. 69.
    Gadir N, Haim-Vilmovsky L, Kraut-Cohen J et al (2011) Localization of mRNAs coding for mitochondrial proteins in the yeast Saccharomyces cerevisiae. RNA 17(8):1551–1565.  https://doi.org/10.1261/rna.2621111 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Saint-Georges Y, Garcia M, Delaveau T et al (2008) Yeast mitochondrial biogenesis: a role for the PUF RNA-binding protein Puf3p in mRNA localization. PLoS One 3(6):e2293.  https://doi.org/10.1371/journal.pone.0002293 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Eliyahu E, Pnueli L, Melamed D et al (2010) Tom20 mediates localization of mRNAs to mitochondria in a translation-dependent manner. Mol Cell Biol 30(1):284–294.  https://doi.org/10.1128/MCB.00651-09 CrossRefPubMedGoogle Scholar
  72. 72.
    Zabezhinsky D, Slobodin B, Rapaport D et al (2016) An essential role for COPI in mRNA localization to mitochondria and mitochondrial function. Cell Rep 15(3):540–549.  https://doi.org/10.1016/j.celrep.2016.03.053 CrossRefPubMedGoogle Scholar
  73. 73.
    Lesnik C, Cohen Y, Atir-Lande A et al (2014) OM14 is a mitochondrial receptor for cytosolic ribosomes that supports co-translational import into mitochondria. Nat Commun 5:5711.  https://doi.org/10.1038/ncomms6711 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Ponce-Rojas JC, Avendaño-Monsalve MC, Yañez-Falcón AR et al (2017) αβ‘-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import. FEBS J 284(5):814–830.  https://doi.org/10.1111/febs.14024 CrossRefPubMedGoogle Scholar
  75. 75.
    Gamerdinger M, Hanebuth MA, Frickey T et al (2015) The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum. Science 348(6231):201–207.  https://doi.org/10.1126/science.aaa5335 CrossRefPubMedGoogle Scholar
  76. 76.
    Williams CC, Jan CH, Weissman JS (2014) Targeting and plasticity of mitochondrial proteins revealed by proximity-specific ribosome profiling. Science 346(6210):748–751.  https://doi.org/10.1126/science.1257522 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Jan CH, Williams CC, Weissman JS (2014) Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling. Science 346(6210):1257521.  https://doi.org/10.1126/science.1257521 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Karniely S, Regev-Rudzki N, Pines O (2006) The presequence of fumarase is exposed to the cytosol during import into mitochondria. J Mol Biol 358(2):396–405.  https://doi.org/10.1016/j.jmb.2006.02.023 CrossRefPubMedGoogle Scholar
  79. 79.
    Yogev O, Karniely S, Pines O (2007) Translation-coupled translocation of yeast fumarase into mitochondria in vivo. J Biol Chem 282(40):29222–29229.  https://doi.org/10.1074/jbc.M704201200 CrossRefPubMedGoogle Scholar
  80. 80.
    Sass E, Karniely S, Pines O (2003) Folding of fumarase during mitochondrial import determines its dual targeting in yeast. J Biol Chem 278(46):45109–45116.  https://doi.org/10.1074/jbc.M302344200 CrossRefPubMedGoogle Scholar
  81. 81.
    Hansen KG, Aviram N, Laborenz J et al (2018) An ER surface retrieval pathway safeguards the import of mitochondrial membrane proteins in yeast. Science 361(6407):1118–1122.  https://doi.org/10.1126/science.aar8174 CrossRefPubMedGoogle Scholar
  82. 82.
    Papic D, Elbaz-Alon Y, Koerdt SN et al (2013) The role of Djp1 in import of the mitochondrial protein Mim1 demonstrates specificity between a cochaperone and its substrate protein. Mol Cell Biol 33(20):4083–4094.  https://doi.org/10.1128/MCB.00227-13 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Jeong H, Park J, Jun Y et al (2017) Crystal structures of Mmm1 and Mdm12-Mmm1 reveal mechanistic insight into phospholipid trafficking at ER-mitochondria contact sites. Proc Natl Acad Sci USA 114(45):E9502–E9511.  https://doi.org/10.1073/pnas.1715592114 CrossRefPubMedGoogle Scholar
  84. 84.
    Hirabayashi Y, Kwon S-K, Paek H et al (2017) ER-mitochondria tethering by PDZD8 regulates Ca2 + dynamics in mammalian neurons. Science 358(6363):623–630.  https://doi.org/10.1126/science.aan6009 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    John Peter AT, Herrmann B, Antunes D et al (2017) Vps13-Mcp1 interact at vacuole-mitochondria interfaces and bypass ER-mitochondria contact sites. J Cell Biol 216(10):3219–3229.  https://doi.org/10.1083/jcb.201610055 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Kornmann B, Currie E, Collins SR et al (2009) An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 325(5939):477–481.  https://doi.org/10.1126/science.1175088 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Costa EA, Subramanian K, Nunnari J et al (2018) Defining the physiological role of SRP in protein-targeting efficiency and specificity. Science 359(6376):689–692.  https://doi.org/10.1126/science.aar3607 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Vitali DG, Sinzel M, Bulthuis EP et al (2018) The GET pathway can increase the risk of mitochondrial outer membrane proteins to be mistargeted to the ER. J Cell Sci 131(10):jcs211110.  https://doi.org/10.1242/jcs.211110 CrossRefPubMedGoogle Scholar
  89. 89.
    Kaewsapsak P, Shechner DM, Mallard W et al (2017) Live-cell mapping of organelle-associated RNAs via proximity biotinylation combined with protein-RNA crosslinking. Elife 6:e29224.  https://doi.org/10.7554/eLife.29224 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Aviram N, Ast T, Costa EA et al (2016) The SND proteins constitute an alternative targeting route to the endoplasmic reticulum. Nature 540(7631):134–138.  https://doi.org/10.1038/nature20169 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Schuldiner M, Metz J, Schmid V et al (2008) The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell 134(4):634–645.  https://doi.org/10.1016/j.cell.2008.06.025 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Bausewein T, Mills DJ, Langer JD et al (2017) Cryo-EM structure of the TOM core complex from Neurospora crassa. Cell 170(4):693–700.e7.  https://doi.org/10.1016/j.cell.2017.07.012 CrossRefPubMedGoogle Scholar
  93. 93.
    Model K, Meisinger C, Kühlbrandt W (2008) Cryo-electron microscopy structure of a yeast mitochondrial preprotein translocase. J Mol Biol 383(5):1049–1057.  https://doi.org/10.1016/j.jmb.2008.07.087 CrossRefPubMedGoogle Scholar
  94. 94.
    Shiota T, Imai K, Qiu J et al (2015) Molecular architecture of the active mitochondrial protein gate. Science 349(6255):1544–1548.  https://doi.org/10.1126/science.aac6428 CrossRefPubMedGoogle Scholar
  95. 95.
    Yamamoto H, Fukui K, Takahashi H et al (2009) Roles of Tom70 in import of presequence-containing mitochondrial proteins. J Biol Chem 284(46):31635–31646.  https://doi.org/10.1074/jbc.M109.041756 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Backes S, Herrmann JM (2017) Protein translocation into the intermembrane space and matrix of mitochondria: mechanisms and driving forces. Front Mol Biosci 4:83.  https://doi.org/10.3389/fmolb.2017.00083 CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Melin J, Kilisch M, Neumann P et al (2015) A presequence-binding groove in Tom70 supports import of Mdl1 into mitochondria. Biochim Biophys Acta 1853(8):1850–1859.  https://doi.org/10.1016/j.bbamcr.2015.04.021 CrossRefPubMedGoogle Scholar
  98. 98.
    Fan ACY, Kozlov G, Hoegl A et al (2011) Interaction between the human mitochondrial import receptors Tom20 and Tom70 in vitro suggests a chaperone displacement mechanism. J Biol Chem 286(37):32208–32219.  https://doi.org/10.1074/jbc.M111.280446 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Abe Y, Shodai T, Muto T et al (2000) Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100(5):551–560.  https://doi.org/10.1016/S0092-8674(00)80691-1 CrossRefPubMedGoogle Scholar
  100. 100.
    Yamamoto H, Itoh N, Kawano S et al (2011) Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondria. Proc Natl Acad Sci USA 108(1):91–96.  https://doi.org/10.1073/pnas.1014918108 CrossRefPubMedGoogle Scholar
  101. 101.
    Perry AJ, Hulett JM, Likić VA et al (2006) Convergent evolution of receptors for protein import into mitochondria. Curr Biol 16(3):221–229.  https://doi.org/10.1016/j.cub.2005.12.034 CrossRefPubMedGoogle Scholar
  102. 102.
    Garg S, Stölting J, Zimorski V et al (2015) Conservation of transit peptide-independent protein import into the mitochondrial and hydrogenosomal matrix. Genome Biol Evol 7(9):2716–2726.  https://doi.org/10.1093/gbe/evv175 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Mani J, Desy S, Niemann M et al (2015) Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun 6:6646.  https://doi.org/10.1038/ncomms7646 CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Harbauer AB, Opalińska M, Gerbeth C et al (2014) Mitochondria. Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science 346(6213):1109–1113.  https://doi.org/10.1126/science.1261253 CrossRefPubMedGoogle Scholar
  105. 105.
    Schmidt O, Harbauer AB, Rao S et al (2011) Regulation of mitochondrial protein import by cytosolic kinases. Cell 144(2):227–239.  https://doi.org/10.1016/j.cell.2010.12.015 CrossRefPubMedGoogle Scholar
  106. 106.
    Esaki M, Shimizu H, Ono T et al (2004) Mitochondrial protein import. Requirement of presequence elements and tom components for precursor binding to the TOM complex. J Biol Chem 279(44):45701–45707.  https://doi.org/10.1074/jbc.M404591200 CrossRefPubMedGoogle Scholar
  107. 107.
    Komiya T, Rospert S, Koehler C et al (1998) Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: evidence for the ‘acid chain’ hypothesis. EMBO J 17(14):3886–3898.  https://doi.org/10.1093/emboj/17.14.3886 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Chacinska A, Koehler CM, Milenkovic D et al (2009) Importing mitochondrial proteins: machineries and mechanisms. Cell 138(4):628–644.  https://doi.org/10.1016/j.cell.2009.08.005 CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Neupert W, Herrmann JM (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723–749.  https://doi.org/10.1146/annurev.biochem.76.052705.163409 CrossRefPubMedGoogle Scholar
  110. 110.
    Melin J, Schulz C, Wrobel L et al (2014) Presequence recognition by the tom40 channel contributes to precursor translocation into the mitochondrial matrix. Mol Cell Biol 34(18):3473–3485.  https://doi.org/10.1128/MCB.00433-14 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Albrecht R, Rehling P, Chacinska A et al (2006) The Tim21 binding domain connects the preprotein translocases of both mitochondrial membranes. EMBO Rep 7(12):1233–1238.  https://doi.org/10.1038/sj.embor.7400828 CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Shiota T, Mabuchi H, Tanaka-Yamano S et al (2011) In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22 at work. Proc Natl Acad Sci USA 108(37):15179–15183.  https://doi.org/10.1073/pnas.1105921108 CrossRefPubMedGoogle Scholar
  113. 113.
    Mokranjac D, Paschen SA, Kozany C et al (2003) Tim50, a novel component of the TIM23 preprotein translocase of mitochondria. EMBO J 22(4):816–825.  https://doi.org/10.1093/emboj/cdg090 CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Ramesh A, Peleh V, Martinez-Caballero S et al (2016) A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J Cell Biol 214(4):417–431.  https://doi.org/10.1083/jcb.201602074 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Demishtein-Zohary K, Günsel U, Marom M et al (2017) Role of Tim17 in coupling the import motor to the translocation channel of the mitochondrial presequence translocase. Elife 6:e22696.  https://doi.org/10.7554/eLife.22696 CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Demishtein-Zohary K, Marom M, Neupert W et al (2015) GxxxG motifs hold the TIM23 complex together. FEBS J 282(11):2178–2186.  https://doi.org/10.1111/febs.13266 CrossRefPubMedGoogle Scholar
  117. 117.
    Schendzielorz AB, Schulz C, Lytovchenko O et al (2017) Two distinct membrane potential-dependent steps drive mitochondrial matrix protein translocation. J Cell Biol 216(1):83–92.  https://doi.org/10.1083/jcb.201607066 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Meinecke M, Wagner R, Kovermann P et al (2006) Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science 312(5779):1523–1526.  https://doi.org/10.1126/science.1127628 CrossRefPubMedGoogle Scholar
  119. 119.
    Lytovchenko O, Melin J, Schulz C et al (2013) Signal recognition initiates reorganization of the presequence translocase during protein import. EMBO J 32(6):886–898.  https://doi.org/10.1038/emboj.2013.23 CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Chacinska A, Lind M, Frazier AE et al (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120(6):817–829.  https://doi.org/10.1016/j.cell.2005.01.011 CrossRefPubMedGoogle Scholar
  121. 121.
    Los Rios P de, Ben-Zvi A, Slutsky O et al (2006) Hsp70 chaperones accelerate protein translocation and the unfolding of stable protein aggregates by entropic pulling. Proc Natl Acad Sci USA 103(16):6166–6171.  https://doi.org/10.1073/pnas.0510496103 CrossRefPubMedGoogle Scholar
  122. 122.
    Ting S-Y, Yan NL, Schilke BA et al (2017) Dual interaction of scaffold protein Tim44 of mitochondrial import motor with channel-forming translocase subunit Tim23. Elife 6:e23609.  https://doi.org/10.7554/eLife.23609 CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Miyata N, Tang Z, Conti MA et al (2017) Adaptation of a genetic screen reveals an inhibitor for mitochondrial protein import component Tim44. J Biol Chem 292(13):5429–5442.  https://doi.org/10.1074/jbc.M116.770131 CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Banerjee R, Gladkova C, Mapa K et al (2015) Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein. Elife 4:e11897.  https://doi.org/10.7554/eLife.11897 CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    D’Silva PD, Schilke B, Walter W et al (2003) J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix. Proc Natl Acad Sci USA 100(24):13839–13844.  https://doi.org/10.1073/pnas.1936150100 CrossRefPubMedGoogle Scholar
  126. 126.
    Krayl M, Lim JH, Martin F et al (2007) A cooperative action of the ATP-dependent import motor complex and the inner membrane potential drives mitochondrial preprotein import. Mol Cell Biol 27(2):411–425.  https://doi.org/10.1128/MCB.01391-06 CrossRefPubMedGoogle Scholar
  127. 127.
    Burkhart JM, Taskin AA, Zahedi RP et al (2015) Quantitative profiling for substrates of the mitochondrial presequence processing protease reveals a set of nonsubstrate proteins increased upon proteotoxic stress. J Proteome Res 14(11):4550–4563.  https://doi.org/10.1021/acs.jproteome.5b00327 CrossRefPubMedGoogle Scholar
  128. 128.
    Ieva R, Schrempp SG, Opaliński L et al (2014) Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane. Mol Cell 56(5):641–652.  https://doi.org/10.1016/j.molcel.2014.10.010 CrossRefPubMedGoogle Scholar
  129. 129.
    Bömer U, Meijer M, Guiard B et al (1997) The sorting route of cytochrome b2 branches from the general mitochondrial import pathway at the preprotein translocase of the inner membrane. J Biol Chem 272(48):30439–30446.  https://doi.org/10.1074/jbc.272.48.30439 CrossRefPubMedGoogle Scholar
  130. 130.
    Rojo EE, Guiard B, Neupert W et al (1998) Sorting of D-lactate dehydrogenase to the inner membrane of mitochondria. Analysis of topogenic signal and energetic requirements. J Biol Chem 273(14):8040–8047CrossRefPubMedGoogle Scholar
  131. 131.
    Zanphorlin LM, Lima TB, Wong MJ et al (2016) Heat shock protein 90 kDa (Hsp90) has a second functional interaction site with the mitochondrial import receptor Tom70. J Biol Chem 291(36):18620–18631.  https://doi.org/10.1074/jbc.M115.710137 CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Webb CT, Gorman MA, Lazarou M et al (2006) Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol Cell 21(1):123–133.  https://doi.org/10.1016/j.molcel.2005.11.010 CrossRefPubMedGoogle Scholar
  133. 133.
    Baker MJ, Webb CT, Stroud DA et al (2009) Structural and functional requirements for activity of the Tim9–Tim10 complex in mitochondrial protein import. Mol Biol Cell 20(3):769–779.  https://doi.org/10.1091/mbc.E08-09-0903 CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Hasson SA, Damoiseaux R, Glavin JD et al (2010) Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation. Proc Natl Acad Sci USA 107(21):9578–9583.  https://doi.org/10.1073/pnas.0914387107 CrossRefPubMedGoogle Scholar
  135. 135.
    Weinhäupl K, Lindau C, Hessel A et al (2018) Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space. Cell 175(5):1365–1379.e25.  https://doi.org/10.1016/j.cell.2018.10.039 CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Sirrenberg C, Endres M, Fölsch H et al (1998) Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature 391:912.  https://doi.org/10.1038/36136 CrossRefPubMedGoogle Scholar
  137. 137.
    Callegari S, Richter F, Chojnacka K et al (2016) TIM29 is a subunit of the human carrier translocase required for protein transport. FEBS Lett 590(23):4147–4158.  https://doi.org/10.1002/1873-3468.12450 CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Kang Y, Baker MJ, Liem M et al (2016) Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability. Elife.  https://doi.org/10.7554/eLife.17463 CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Pacheu-Grau D, Callegari S, Emperador S et al (2018) Mutations of the mitochondrial carrier translocase channel subunit TIM22 cause early-onset mitochondrial myopathy. Hum Mol Genet 27(23):4135–4144.  https://doi.org/10.1093/hmg/ddy305 CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Kang Y, Stroud DA, Baker MJ et al (2017) Sengers syndrome-associated mitochondrial acylglycerol kinase is a subunit of the human TIM22 protein import complex. Mol Cell 67(3):457–470.e5.  https://doi.org/10.1016/j.molcel.2017.06.014 CrossRefPubMedGoogle Scholar
  141. 141.
    Vukotic M, Nolte H, König T et al (2017) Acylglycerol kinase mutated in sengers syndrome is a subunit of the TIM22 protein translocase in mitochondria. Mol Cell 67(3):471–483.e7.  https://doi.org/10.1016/j.molcel.2017.06.013 CrossRefPubMedGoogle Scholar
  142. 142.
    Gebert N, Gebert M, Oeljeklaus S et al (2011) Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of the mitochondrial inner membrane. Mol Cell 44(5):811–818.  https://doi.org/10.1016/j.molcel.2011.09.025 CrossRefPubMedGoogle Scholar
  143. 143.
    Höhr AIC, Lindau C, Wirth C et al (2018) Membrane protein insertion through a mitochondrial β-barrel gate. Science 359(6373):eaah6834.  https://doi.org/10.1126/science.aah6834 CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Wiedemann N, Kozjak V, Chacinska A et al (2003) Machinery for protein sorting and assembly in the mitochondrial outer membrane. Nature 424:565.  https://doi.org/10.1038/nature01753 CrossRefPubMedGoogle Scholar
  145. 145.
    Becker T, Guiard B, Thornton N et al (2010) Assembly of the mitochondrial protein import channel: role of Tom5 in two-stage interaction of Tom40 with the SAM complex. Mol Biol Cell 21(18):3106–3113.  https://doi.org/10.1091/mbc.E10-06-0518 CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Mesecke N, Terziyska N, Kozany C et al (2005) A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell 121(7):1059–1069.  https://doi.org/10.1016/j.cell.2005.04.011 CrossRefPubMedGoogle Scholar
  147. 147.
    Banci L, Bertini I, Ciofi-Baffoni S et al (2012) Structural characterization of CHCHD5 and CHCHD7: two atypical human twin CX9C proteins. J Struct Biol 180(1):190–200.  https://doi.org/10.1016/j.jsb.2012.07.007 CrossRefPubMedGoogle Scholar
  148. 148.
    Hofmann S, Rothbauer U, Mühlenbein N et al (2005) Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space. J Mol Biol 353(3):517–528.  https://doi.org/10.1016/j.jmb.2005.08.064 CrossRefPubMedGoogle Scholar
  149. 149.
    Klöppel C, Suzuki Y, Kojer K et al (2011) Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol. Mol Biol Cell 22(20):3749–3757.  https://doi.org/10.1091/mbc.E11-04-0293 CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Terziyska N, Grumbt B, Kozany C et al (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(3):1353–1363.  https://doi.org/10.1074/jbc.M805035200 CrossRefPubMedGoogle Scholar
  151. 151.
    Fischer M, Horn S, Belkacemi A et al (2013) Protein import and oxidative folding in the mitochondrial intermembrane space of intact mammalian cells. Mol Biol Cell 24(14):2160–2170.  https://doi.org/10.1091/mbc.E12-12-0862 CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Weckbecker D, Longen S, Riemer J et al (2012) Atp23 biogenesis reveals a chaperone-like folding activity of Mia40 in the IMS of mitochondria. EMBO J 31(22):4348–4358.  https://doi.org/10.1038/emboj.2012.263 CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Petrungaro C, Zimmermann KM, Küttner V et al (2015) The Ca(2+)-Dependent Release of the Mia40-Induced MICU1-MICU2 Dimer from MCU Regulates Mitochondrial Ca(2+) Uptake. Cell Metab 22(4):721–733.  https://doi.org/10.1016/j.cmet.2015.08.019 CrossRefPubMedGoogle Scholar
  154. 154.
    Wurm CA, Neumann D, Lauterbach MA et al (2011) Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient. Proc Natl Acad Sci USA 108(33):13546–13551.  https://doi.org/10.1073/pnas.1107553108 CrossRefPubMedGoogle Scholar
  155. 155.
    Bohnert M, Zerbes RM, Davies KM et al (2015) Central role of Mic10 in the mitochondrial contact site and cristae organizing system. Cell Metab 21(5):747–755.  https://doi.org/10.1016/j.cmet.2015.04.007 CrossRefPubMedGoogle Scholar
  156. 156.
    Barbot M, Jans DC, Schulz C et al (2015) Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions. Cell Metab 21(5):756–763.  https://doi.org/10.1016/j.cmet.2015.04.006 CrossRefPubMedGoogle Scholar
  157. 157.
    Körner C, Barrera M, Dukanovic J et al (2012) The C-terminal domain of Fcj1 is required for formation of crista junctions and interacts with the TOB/SAM complex in mitochondria. Mol Biol Cell 23(11):2143–2155.  https://doi.org/10.1091/mbc.E11-10-0831 CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Herrmann JM (2011) MINOS is plus: a Mitofilin complex for mitochondrial membrane contacts. Dev Cell 21(4):599–600.  https://doi.org/10.1016/j.devcel.2011.09.013 CrossRefPubMedGoogle Scholar
  159. 159.
    Varabyova A, Topf U, Kwiatkowska P et al (2013) Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1. FEBS J 280(20):4943–4959.  https://doi.org/10.1111/febs.12409 CrossRefPubMedGoogle Scholar
  160. 160.
    Malsburg K von der, Müller JM, Bohnert M et al (2011) Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis. Dev Cell 21(4):694–707.  https://doi.org/10.1016/j.devcel.2011.08.026 CrossRefPubMedGoogle Scholar
  161. 161.
    Waegemann K, Popov-Čeleketić D, Neupert W et al (2015) Cooperation of TOM and TIM23 complexes during translocation of proteins into mitochondria. J Mol Biol 427(5):1075–1084.  https://doi.org/10.1016/j.jmb.2014.07.015 CrossRefPubMedGoogle Scholar
  162. 162.
    Ellenrieder L, Opaliński Ł, Becker L et al (2016) Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10. Nat Commun 7:13021.  https://doi.org/10.1038/ncomms13021 CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Flinner N, Ellenrieder L, Stiller SB et al (2013) Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex. Biochim Biophys Acta 1833(12):3314–3325.  https://doi.org/10.1016/j.bbamcr.2013.10.006 CrossRefPubMedGoogle Scholar
  164. 164.
    Wideman JG, Go NE, Klein A et al (2010) Roles of the Mdm10, Tom7, Mdm12, and Mmm1 proteins in the assembly of mitochondrial outer membrane proteins in Neurospora crassa. Mol Biol Cell 21(10):1725–1736.  https://doi.org/10.1091/mbc.e09-10-0844 CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Elbaz-Alon Y, Eisenberg-Bord M, Shinder V et al (2015) Lam6 regulates the extent of contacts between organelles. Cell Rep 12(1):7–14.  https://doi.org/10.1016/j.celrep.2015.06.022 CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    González Montoro A, Auffarth K, Hönscher C et al (2018) Vps39 interacts with Tom40 to establish one of two functionally distinct vacuole-mitochondria contact sites. Dev Cell 45(5):621–636.e7.  https://doi.org/10.1016/j.devcel.2018.05.011 CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cell BiologyUniversity of KaiserslauternKaiserslauternGermany

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