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Quality control of proteins in the mitochondrion

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Chaperones

Part of the book series: Topics in Current Genetics ((TCG,volume 16))

Abstract

The quality control of proteins within mitochondria is ensured by conserved and ubiquitous ATP-dependent molecular chaperones and proteases, present in various subcompartments of the organelle. Hsp70 chaperones drive protein import and facilitate folding of newly imported preproteins, but are also required for proteolysis of misfolded polypeptides by ATP-dependent proteases. Energy dependent proteases in mitochondria include Lon and Clp proteases in the matrix space and two AAA proteases in the inner membrane, all of them compartmental proteases of the AAA+ family with chaperone-like properties. Studies in yeast identify essential regulatory roles of these proteases for mitochondrial genome integrity, gene expression, the assembly of the respiratory chain, and mitochondrial morphology. An impaired proteolytic system in mitochondria has been identified as a cause for neurodegeneration in human. The present review summarizes the current understanding of the protein quality system in mitochondria and discusses the molecular action of protein machineries involved.

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References

  • 1. Abeliovich H, Klionsky DJ (2001) Autophagy in yeast: mechanistic insights and physiological function. Microbiol Mol Biol Rev 65:463-479

    Article  PubMed  CAS  Google Scholar 

  • 2. Adam Z, Adamska I, Nakabayashi K, Ostersetzer O, Haussuhl K, Manuell A, Zheng B, Vallon O, Rodermel SR, Shinozaki K, Clarke AK (2001) Chloroplast and mitochondrial proteases an Arabidopsis. A proposed nomenclature. Plant Physiol 125:1912-1918

    Article  PubMed  CAS  Google Scholar 

  • 3. Ahnert P, Picha KM, Patel SS (2000) A ring-opening mechanism for DNA binding in the central channel of the T7 helicase-primase protein. EMBO J 19:3418-3427

    Article  PubMed  CAS  Google Scholar 

  • 4. Arlt H, Steglich G, Perryman R, Guiard B, Neupert W, Langer T (1998) The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease. EMBO J 17:4837-4847

    Article  PubMed  CAS  Google Scholar 

  • 5. Arlt H, Tauer R, Feldmann H, Neupert W, Langer T (1996) The YTA10-12-complex, an AAA protease with chaperone-like activity in the inner membrane of mitochondria. Cell 85:875-885

    Article  PubMed  CAS  Google Scholar 

  • 6. Artal-Sanz M, Tsang WY, Willems EM, Grivell LA, Lemire BD, van der Spek H, Nijtmans LG, Sanz MA (2003) The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans. J Biol Chem 278:32091-32099

    Article  PubMed  CAS  Google Scholar 

  • 7. Atorino L, Silvestri L, Koppen M, Cassina L, Ballabio A, Marconi R, Langer T, Casari G (2003) Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia. J Cell Biol 163:777-787

    Article  PubMed  CAS  Google Scholar 

  • 8. Augustin S, Nolden M, Müller S, Hardt O, Arnold I, Langer T (2005) Characterization of peptides released from mitochondria: evidence for constant proteolysis and peptide efflux. J Biol Chem 280:2691-2699

    Article  PubMed  CAS  Google Scholar 

  • 9. Banfi S, Bassi MT, Andolfi G, Marchitiello A, Zanotta S, Ballabio A, Casari G, Franco B (1999) Identification and characterization of AFG3L2, a novel paraplegin-related gene. Genomics 59:51-58

    Article  PubMed  CAS  Google Scholar 

  • 10. Barakat S, Pearce DA, Sherman F, Rapp WD (1998) Maize contains a Lon protease gene that can partially complement a yeast pim1-deletion mutant. Plant Mol Biol 37:141-154

    Article  PubMed  CAS  Google Scholar 

  • 11. Bateman JM, Iacovino M, Perlman PS, Butow RA (2002) Mitochondrial DNA instability mutants of the bifunctional protein Ilv5p have altered organization in mitochondria and are targeted for degradation by Hsp78 and the Pim1p protease. J Biol Chem 277:47946-47953

    Article  PubMed  CAS  Google Scholar 

  • 12. Bota DA, Davies KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell Biol 4:674-680

    Article  PubMed  CAS  Google Scholar 

  • 13. Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351-366

    Article  PubMed  CAS  Google Scholar 

  • 14. Burger G, Gray MW, Lang BF (2003) Mitochondrial genomes: anything goes. Trends Genet 19:709-716

    Article  PubMed  CAS  Google Scholar 

  • 15. Butow RA, Avadhani NG (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14:1-15

    Article  PubMed  CAS  Google Scholar 

  • 16. Campbell CL, Tanaka N, White KH, Thorsness PE (1994) Mitochondrial morphological and functional defects in yeast caused by yme1 are suppressed by mutation of a 26S protease subunit homologue. Mol Biol Cell 5:899-905

    PubMed  CAS  Google Scholar 

  • 17. Campbell CL, Thorsness PE (1998) Escape of mitochondrial DNA to the nucleus in yme1 yeast is mediated by vacuolar-dependent turnover of abnormal mitochondrial compartments. J Cell Sci 111:2455-2464

    PubMed  CAS  Google Scholar 

  • 18. Casari G, De-Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, DeMichele G, Filla A, Cocozza S, Marconi R, Durr A, Fontaine B, Ballabio A (1998) Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93:973-983

    Article  PubMed  CAS  Google Scholar 

  • 19. Charette MF, Henderson GW, Doane LL, Markovitz A (1984) DNA-stimulated ATPase activity on the lon (CapR) protein. J Bacteriol 158:195-201

    PubMed  CAS  Google Scholar 

  • 20. Chung CH, Goldberg AL (1982) DNA stimulates ATP-dependent proteolysis and protein-dependent ATPase activity of protease La from Escherichia coli. Proc Natl Acad Sci USA 79:795-799

    Article  PubMed  CAS  Google Scholar 

  • 21. Corydon TJ, Bross P, Holst HU, Neve S, Kristiansen K, Gregersen N, Bolund L (1998) A human homologue of Escherichia coli ClpP caseinolytic protease: recombinant expression, intracellular processing and subcellular localization. Biochem J 331:309-316

    PubMed  CAS  Google Scholar 

  • 22. Corydon TJ, Wilsbech M, Jespersgaard C, Andresen BS, Borglum AD, Pederson S, Bolund L, Gregersen N, Bross P (2000) Human and mouse mitochondrial orthologs of bacterial clpX. Mamm Genome 11:899-905

    Article  PubMed  CAS  Google Scholar 

  • 23. Craig EA, Kramer J, Shilling J, Werner-Washburne M, Holmes S, Kosic-Smithers J, Nicolet CM (1989) SSC1, an essential member of the yeast HSP70 multigene family, encodes a mitochondrial protein. Mol Cell Biol 9:3000-3008

    PubMed  CAS  Google Scholar 

  • 24. Desautels M, Goldberg AL (1982) Liver mitochondria contain an ATP-dependent, vanadate-sensitive pathway for the degradation of proteins. Proc Natl Acad Sci USA 79:1869-1873

    Article  PubMed  CAS  Google Scholar 

  • 25. Epstein CB, Waddle JA, Hale W, Davé V, Thornton J, Macatee TL, Garner HR, Butow RA (2001) Genome-wide responses to mitochondrial dysfunction. Mol Biol Cell 12:297-308

    PubMed  CAS  Google Scholar 

  • 26. Esnault Y, Feldheim D, Blondel MO, Schekman R, Képès F (1994) SSS1 encodes a stabilizing component of the Sec61 subcomplex of the yeast protein translocation apparatus. J Biol Chem 269:27478-27485

    PubMed  CAS  Google Scholar 

  • 27. Esser K, Tursun B, Ingenhoven M, Michaelis G, Pratje E (2002) A novel two-step mechanism for removal of a mitochondrial signal sequence involves the m-AAA complex and the putative rhomboid protease Pcp1. J Mol Biol 323:835-843

    Article  PubMed  CAS  Google Scholar 

  • 28. Ferreirinha F, Quattrini A, Priozzi M, Valsecchi V, Dina G, Broccoli V, Auricchio A, Piemonte F, Tozzi G, Gaeta L, Casari G, Ballabio A, Rugarli EI (2004) Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J Clin Invest 113:231-242

    Article  PubMed  CAS  Google Scholar 

  • 29. Frazier AE, Dudek J, Guiard B, Voos W, Li Y, Lind M, Meisinger C, Geissler A, Sickmann A, Meyer HE, Bilanchone V, Cumsky MG, Truscott KN, Pfanner N, Rehling P (2004) Pam16 has an essential role in the mitochondrial protein import motor. Nat Struct Mol Biol 11:226-233

    Article  PubMed  CAS  Google Scholar 

  • 30. Frickey T, Lupas AN (2004) Phylogenetic analysis of AAA proteins. J Struct Biol 146:2-10

    Article  PubMed  CAS  Google Scholar 

  • 31. Fu GK, Markovitz DM (1998) The human Lon protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner. Biochemistry 37:1905-1909

    Article  PubMed  CAS  Google Scholar 

  • 32. Fu GK, Smith MJ, Markovitz DM (1997) Bacterial protease Lon is a site-specific DNA-binding protein. J Biol Chem 272:534-538

    Article  PubMed  CAS  Google Scholar 

  • 33. Galluhn D, Langer T (2004) Reversible assembly of the ATP-binding cassette transporter Mdl1 with the F1FO-ATP synthase in mitochondria. J Biol Chem 279:38338-38345

    Article  PubMed  CAS  Google Scholar 

  • 34. Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN (2003) Composition and dynamics of human mitochondrial nucleoids. Mol Biol Cell 14:1583-1596

    Article  PubMed  CAS  Google Scholar 

  • 35. Germaniuk A, Liberek K, Marszalek J (2002) A bichaperone (Hsp70-Hsp78) system restores mitochondrial DNA synthesis following thermal inactivation of Mip1p polymerase. J Biol Chem 277:27801-27808

    Article  PubMed  CAS  Google Scholar 

  • 36. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895-899

    Article  PubMed  CAS  Google Scholar 

  • 37. Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891-2906

    Article  PubMed  CAS  Google Scholar 

  • 38. Guélin E, Rep M, Grivell LA (1994) Sequence of the AFG3 gene encoding a new member of the FtsH/Yme1/Tma subfamily of the AAA-protein family. Yeast 10:1389-1394

    Article  Google Scholar 

  • 39. Guélin E, Rep M, Grivell LA (1996) Afg3p, a mitochondrial ATP-dependent metalloprotease, is involved in the degradation of mitochondrially-encoded Cox1, Cox3, Cob, Su6, Su8, and Su9 subunits of the inner membrane complexes III, IV, and V. FEBS Lett 381:42-46

    Article  Google Scholar 

  • 40. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714-2723

    Article  PubMed  CAS  Google Scholar 

  • 41. Halperin T, Zheng B, Itzhaki H, Clarke AK, Adam Z (2001) Plant mitochondria contain proteolytic and regulatory subunits of the ATP-dependent Clp protease. Plant Mol Biol 45:461-468

    Article  PubMed  CAS  Google Scholar 

  • 42. Hampton RY (2002) ER-associated degradation in protein quality control and cellular regulation. Curr Opin Cell Biol 14:476-482

    Article  PubMed  CAS  Google Scholar 

  • 43. Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852-1858

    Article  PubMed  CAS  Google Scholar 

  • 44. Herlan M, Vogel F, Bornhövd C, Neupert W, Reichert AS (2003) Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA. J Biol Chem 278:27781-27788

    Article  PubMed  CAS  Google Scholar 

  • 45. Herman C, Prakash S, Lu CZ, Matouschek A, Gross CA (2003) Lack of a robust unfoldase activity confers a unique level of substrate specificity to the universal AAA protease FtsH. Mol Cell 11:659-669

    Article  PubMed  CAS  Google Scholar 

  • 46. Hohfeld J, Cyr DM, Patterson C (2001) From the cradle to the grave: molecular chaperones that may choose between folding and degradation. EMBO Rep 2:885-890

    Article  PubMed  CAS  Google Scholar 

  • 47. Hori O, Ichinoda F, Tamatani T, Yamaguchi A, Sato N, Ozawa K, Kitao Y, Miyazaki M, Harding HP, Ron D, Tohyama M, Stern DM, Ogawa S (2002) Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease. J Cell Biol 157:1151-1160

    Article  PubMed  CAS  Google Scholar 

  • 48. Horwich AL, Weber-Ban EU, Finley D (1999) Chaperone rings in protein folding and degradation. Proc Natl Acad Sci USA 96:11033-11040

    Article  PubMed  CAS  Google Scholar 

  • 49. Huang WP, Klionsky DJ (2002) Autophagy in yeast: a review of the molecular machinery. Cell Struct Funct 27:409-420

    Article  PubMed  CAS  Google Scholar 

  • 50. Hughes TR, Marton MJ, Jones AR, Roberts CJ, Stoughton R, Armour CD, Bennett HA, Coffey E, Dai H, He YD, Kidd MJ, King AM, Meyer MR, Slade D, Lum PY, Stepaniants SB, Shoemaker DD, Gachotte D, Chakraburtty K, Simon J, Bard M, Friend SH (2000) Functional discovery via a compendium of expression profiles. Cell 102:109-126

    Article  PubMed  CAS  Google Scholar 

  • 51. Ikeda E, Yoshida S, Mitsuzawa H, Uno I, Toh-e A (1994) YGE1 is a yeast homolog of Escherichia coli grpE and is required for maintenance of mitochondrial functions. FEBS Lett 339:265-268

    Article  PubMed  CAS  Google Scholar 

  • 52. Iyer LM, Leipe DD, Koonin EV, Aravind L (2004) Evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol 146:11-31

    Article  PubMed  CAS  Google Scholar 

  • 53. Jarosch E, Lenk U, Sommer T (2003) Endoplasmic reticulum-associated protein degradation. Int Rev Cytol 223:39-81

    PubMed  CAS  Google Scholar 

  • 54. Kang PJ, Ostermann J, Shilling J, Neupert W, Craig EA, Pfanner N (1990) Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature 348:137-143

    Article  PubMed  CAS  Google Scholar 

  • 55. Kang SG, Ortega J, Singh SK, Wang N, Huang NN, Steven AC, Maurizi MR (2002) Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP. J Biol Chem 277:21095-21102

    Article  PubMed  CAS  Google Scholar 

  • 56. Karata K, Inagawa T, Wilkinson AJ, Tatsuta T, Ogura T (1999) Dissecting the role of a conserved motif (the second region of homology) in the AAA family of ATPases. Site-directed mutagenesis of the ATP-dependent protease FtsH. J Biol Chem 274:26225-26232

    Article  PubMed  CAS  Google Scholar 

  • 57. Karata K, Verma CS, Wilkinson AJ, Ogura T (2001) Probing the mechanism of ATP hydrolysis and substrate translocation in the AAA protease FtsH by modelling and mutagenesis. Mol Microbiol 39:890-903

    Article  PubMed  CAS  Google Scholar 

  • 58. Käser M, Kambacheld M, Kisters-Woike B, Langer T (2003) Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease. J Biol Chem 278:46414-46423

    Article  CAS  Google Scholar 

  • 59. Kihara A, Akiyama Y, Ito K (1996) A protease complex in the Escherichia coli plasma membrane: HflKC (HflA) forms a complex with FtsH (HflB), regulating its proteolytic activity against SecY. EMBO J 15:6122-6131

    PubMed  CAS  Google Scholar 

  • 60. Klanner C, Prokisch H, Langer T (2001) MAP-1 and IAP-1, two novel AAA proteases with catalytic sites on opposite membrane surfaces in the mitochondrial inner membrane of Neurospora crassa. Mol Biol Cell 12:2858-2869

    PubMed  CAS  Google Scholar 

  • 61. Kolodziejczak M, Kolaczkowska A, Szczesny B, Urantowka A, Knorpp C, Kieleczawa J, Janska H (2002) A higher plant mitochondrial homologue of the yeast m-AAA protease. Molecular cloning, localization, and putative function. J Biol Chem 277:43792-43798

    Article  PubMed  CAS  Google Scholar 

  • 62. Korbel D, Wurth S, Kaser M, Langer T (2004) Membrane protein turnover by the m-AAA protease in mitochondria depends on the transmembrane domains of its subunits. EMBO Rep 5:698-703

    Article  PubMed  CAS  Google Scholar 

  • 63. Kozany C, Mokranjac D, Sichting M, Neupert W, Hell K (2004) The J domain-related cochaperone Tim16 is a constituent of the mitochondrial TIM23 preprotein translocase. Nat Struct Mol Biol 11:234-241

    Article  PubMed  CAS  Google Scholar 

  • 64. Kremmidiotis G, Gardner AE, Settasatian C, Savoia A, Sutherland GR, Callen DF (2001) Molecular and functional analyses of the human and mouse genes encoding AFG3L1, a mitochondrial metalloprotease homologous to the human spastic paraplegia protein. Genomics 76:58-65

    Article  PubMed  CAS  Google Scholar 

  • 65. Krzewska J, Langer T, Liberek K (2001) Mitochondrial Hsp78, a member of the Clp/Hsp100 family in Saccharomyces cerevisiae, cooperates with Hsp70 in protein refolding. FEBS Lett 489:92-96

    Article  PubMed  CAS  Google Scholar 

  • 66. Kutejová E, Durcová G, Surovková E, Kuzela S (1993) Yeast mitochondrial ATP-dependent protease: purification and comparison with the homologous rat enzyme and the bacterial ATP-dependent protease La. FEBS Lett 329:47-50

    Article  Google Scholar 

  • 67. Kuzmin EV, Karpova OV, Elthon TE, Newton KJ (2004) Mitochondrial respiratory deficiencies signal up-regulation of genes for heat shock proteins. J Biol Chem 279:20672-20677

    Article  PubMed  CAS  Google Scholar 

  • 68. Laloraya S, Dekker PJT, Voos W, Craig EA, Pfanner N (1995) Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and maturation of preproteins. Mol Cell Biol 15:7098-7105

    PubMed  CAS  Google Scholar 

  • 69. Laloraya S, Gambill BD, Craig E (1994) A role for a eukaryotic GrpE-related protein, Mge1p, in protein translocation. Proc Natl Acad Sci USA 91:6481-6485

    Article  PubMed  CAS  Google Scholar 

  • 70. Langer T (2000) AAA proteases - cellular machines for degrading membrane proteins. Trends Biochem Sci 25:207-256

    Article  Google Scholar 

  • 71. Lemaire C, Hamel P, Velours J, Dujardin G (2000) Absence of the mitochondrial AAA protease Yme1p restores FO-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae. J Biol Chem 275:23471-23475

    Article  PubMed  CAS  Google Scholar 

  • 72. Lenzen CU, Steinmann D, Whiteheart SW, Weis WI (1998) Crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein. Cell 94:525-536

    Article  PubMed  CAS  Google Scholar 

  • 73. Leonhard K, Guiard B, Pellechia G, Tzagoloff A, Neupert W, Langer T (2000) Membrane protein degradation by AAA proteases in mitochondria: extraction of substrates from either membrane surface. Mol Cell 5:629-638

    Article  PubMed  CAS  Google Scholar 

  • 74. Leonhard K, Herrmann JM, Stuart RA, Mannhaupt G, Neupert W, Langer T (1996) AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria. EMBO J 15:4218-4229

    PubMed  CAS  Google Scholar 

  • 75. Leonhard K, Stiegler A, Neupert W, Langer T (1999) Chaperone-like activity of the AAA domain of the yeast Yme1 AAA protease. Nature 398:348-351

    Article  PubMed  CAS  Google Scholar 

  • 76. Li M, Baumeister P, Roy B, Phan T, Foti D, Luo S, Lee AS (2000) ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1. Mol Cell Biol 20:5096-5106

    Article  PubMed  CAS  Google Scholar 

  • 77. Li Y, Dudek J, Guiard B, Pfanner N, Rehling P, Voos W (2004) The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18. J Biol Chem 279:38047-38054

    Article  PubMed  CAS  Google Scholar 

  • 78. Liu T, Lu B, Lee I, Ondrovicova G, Kutejova E, Suzuki CK (2004) DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate. J Biol Chem 279:13902-13910

    Article  PubMed  CAS  Google Scholar 

  • 79. Lu B, Liu T, Crosby JA, Thomas-Wohlever J, Lee I, Suzuki CK (2003) The ATP-dependent Lon protease of Mus musculus is a DNA-binding protein that is functionally conserved between yeast and mammals. Gene 306:45-55

    Article  PubMed  CAS  Google Scholar 

  • 80. Lupas AN, Martin J (2002) AAA proteins. Curr Opin Struct Biol 12:746-753

    Article  PubMed  CAS  Google Scholar 

  • 81. Manning-Krieg UC, Scherer PE, Schatz G (1991) Sequential action of mitochondrial chaperones in protein import into the matrix. EMBO J 10:3273-3280

    PubMed  CAS  Google Scholar 

  • 82. Martin J (1997) Molecular chaperones and mitochondrial protein folding. J Bioenerg Biomembr 29:35-43

    Article  PubMed  CAS  Google Scholar 

  • 83. Martinus RD, Garth GP, Webster TL, Cartwright P, Naylor DJ, Hoj PB, Hoogenraad NJ (1996) Selective induction of mitochondrial chaperones in response to loss of the mitochondrial genome. Eur J Biochem 240:98-103

    Article  PubMed  CAS  Google Scholar 

  • 84. Mokranjac D, Sichting M, Neupert W, Hell K (2003) Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J 22:4945-4956

    Article  PubMed  CAS  Google Scholar 

  • 85. Mootha VK, Bunkenborg J, Olsen JV, Hjerrild M, Wisniewski JR, Stahl E, Bolouri MS, Ray HN, Sihag S, Kamal M, Patterson N, Lander ES, Mann M (2003) Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115:629-640

    Article  PubMed  CAS  Google Scholar 

  • 86. Nakai M, Kato Y, Ikeda E, Toh-e A, Endo T (1994) Yge1p, a eukaryotic Grp-E homolog, is localized in the mitochondrial matrix and interacts with mitochondrial Hsp70. Biochem Biophys Res Commun 200:435-442

    Article  PubMed  CAS  Google Scholar 

  • 87. Nakai T, Mera Y, Yasuhara T, Ohashi A (1994) Divalent metal ion-dependent mitochondrial degradation of unassembled subunits 2 and 3 of cytochrome c oxidase. J Biochem (Tokyo) 116:752-758

    Google Scholar 

  • 88. Nakai T, Yasuhara T, Fujiki Y, Ohashi A (1995) Multiple genes, including a member of the AAA family, are essential for the degradation of unassembled subunit 2 of cytochrome c oxidase in yeast mitochondria. Mol Cell Biol 15:4441-4452

    PubMed  CAS  Google Scholar 

  • 89. Neupert W, Brunner M (2002) The protein import motor of mitochondria. Nature Rev Mol Cell Biol 3:555-565

    Article  CAS  Google Scholar 

  • 90. Neuwald AF, Aravind L, Spouge JL, Koonin EV (1999) AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9:27-43

    PubMed  CAS  Google Scholar 

  • 91. Nijtmans LGJ, Artal Sanz M, Grivell LA, Coates PJ (2002) The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease. Cell Mol Life Sci 59:143-155

    Article  PubMed  CAS  Google Scholar 

  • 92. Nijtmans LGJ, de Jong L, Sanz MA, Coates PJ, Berden JA, Back JW, Muijsers AO, Van der Speck H, Grivell LA (2000) Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins. EMBO J 19:2444-2451

    Article  PubMed  CAS  Google Scholar 

  • 93. Niwa H, Tsuchiya D, Makyio H, Yoshida M, Morikawa K (2002) Hexameric ring structure of the ATPase domain of the membrane-integrated metalloprotease FtsH from Thermus thermophilus HB8. Structure (Camb) 10:1415-1423

    Google Scholar 

  • 94. Ogura T, Wilkinson AJ (2001) AAA+ superfamily of ATPases: common structure-diverse function. Genes Cells 6:575-597

    Article  PubMed  CAS  Google Scholar 

  • 95. Ohlmeier S, Kastaniotis AJ, Hiltunen JK, Bergmann U (2004) The yeast mitochondrial proteome, a study of fermentative and respiratory growth. J Biol Chem 279:3956-3979

    Article  PubMed  CAS  Google Scholar 

  • 96. Pajic A, Tauer R, Feldmann H, Neupert W, Langer T (1994) Yta10p is required for the ATP-dependent degradation of polypeptides in the inner membrane of mitochondria. FEBS Lett 353:201-206

    Article  PubMed  CAS  Google Scholar 

  • 97. Paschen SA, Neupert W (2001) Protein import into mitochondria. IUBMB Life 52:101-112

    PubMed  CAS  Google Scholar 

  • 98. Paul MF, Tzagoloff A (1995) Mutations in RCA1 and AFG3 inhibit F1-ATPase assembly in Saccharomyces cerevisiae. FEBS Lett 373:66-70

    Article  PubMed  CAS  Google Scholar 

  • 99. Pearce DA, Sherman F (1995) Degradation of cytochrome oxidase subunits in mutants of yeast lacking cytochrome c and suppression of the degradation by mutation of yme1. J Biol Chem 270:1-4

    Article  Google Scholar 

  • 100. Peltier JB, Ripoll DR, Friso G, Rudella A, Cai Y, Ytterberg J, Giacomelli L, Pillardy J, van Wijk KJ (2004) Clp protease complexes from photosynthetic and non-photosynthetic plastids and mitochondria of plants, their predicted three-dimensional structures, and functional implications. J Biol Chem 279:4768-4781

    Article  PubMed  CAS  Google Scholar 

  • 101. Pickart CM, Cohen RE (2004) Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 5:177-187

    Article  PubMed  CAS  Google Scholar 

  • 102. Prokisch H, Scharfe C, Camp DG, 2nd, Xiao W, David L, Andreoli C, Monroe ME, Moore RJ, Gritsenko MA, Kozany C, Hixson KK, Mottaz HM, Zischka H, Ueffing M, Herman ZS, Davis RW, Meitinger T, Oefner PJ, Smith RD, Steinmetz LM (2004) Integrative analysis of the mitochondrial proteome in yeast. PLoS Biol 2:795-804

    Article  CAS  Google Scholar 

  • 103. Rawlings ND, Barrett AJ (1995) Evolutionary families of metallopeptidases. Methods Enzymol 248:183-228

    Article  PubMed  CAS  Google Scholar 

  • 104. Rehling P, Brandner K, Pfanner N (2004) Mitochondrial import and the twin-pore translocase. Nat Rev Mol Cell Biol 5:519-530

    Article  PubMed  CAS  Google Scholar 

  • 105. Reichert AS, Neupert W (2004) Mitochondriomics or what makes us breathe. Trends Genet 20:555-562

    Article  PubMed  CAS  Google Scholar 

  • 106. Rep M, Nooy J, Guélin E, Grivell LA (1996) Three genes for mitochondrial proteins suppress null-mutations in both AFG3 and RCA1 when overexpressed. Curr Genet 30:206-211

    Article  PubMed  CAS  Google Scholar 

  • 107. Rodriguez-Enriquez S, He L, Lemasters JJ (2004) Role of mitochondrial permeability transition pores in mitochondrial autophagy. Int J Biochem Cell Biol 36:2463-2472

    Article  PubMed  CAS  Google Scholar 

  • 108. Rottgers K, Zufall N, Guiard B, Voos W (2002) The ClpB homolog Hsp78 is required for the efficient degradation of proteins in the mitochondrial matrix. J Biol Chem 277:45829-45837

    Article  PubMed  CAS  Google Scholar 

  • 109. Rowley N, Prip BC, Westermann B, Brown C, Schwarz E, Barrell B, Neupert W (1994) Mdj1p, a novel chaperone of the DnaJ family, is involved in mitochondrial biogenesis and protein folding. Cell 77:249-259

    Article  PubMed  CAS  Google Scholar 

  • 110. Russel SM, Burgess RJ, Mayer RJ (1980) Protein degradation in rat liver during post-natal development. Biochem J 192:321-330

    Google Scholar 

  • 111. Saikawa N, Akiyama Y, Ito K (2004) FtsH exists as an exceptionally large complex containing HflKC in the plasma membrane of Escherichia coli. J Struct Biol 146:123-129

    Article  PubMed  CAS  Google Scholar 

  • 112. Sauer RT, Bolon DN, Burton BM, Burton RE, Flynn JM, Grant RA, Hersch GL, Joshi SA, Kenniston JA, Levchenko I, Neher SB, Oakes ES, Siddiqui SM, Wah DA, Baker TA (2004) Sculpting the proteome with AAA(+) proteases and disassembly machines. Cell 119:9-18

    Article  PubMed  CAS  Google Scholar 

  • 113. Savel'ev AS, Novikova LA, Kovaleva IE, Luzikov VN, Neupert W, Langer T (1998) ATP-dependent proteolysis in mitochondria: m-AAA protease and PIM1 protease exert overlapping substrate specificities and cooperate with the mtHsp70-system. J Biol Chem 273:20596-20602

    Article  Google Scholar 

  • 114. Schmitt M, Neupert W, Langer T (1995) Hsp78, a Clp homologue within mitochondria, can substitute for chaperone functions of mt-hsp70. EMBO J 14:3434-3444

    PubMed  CAS  Google Scholar 

  • 115. Schmitt M, Neupert W, Langer T (1996) The molecular chaperone Hsp78 confers compartment-specific thermotolerance to mitochondria. J Cell Biol 134:1375-1386

    Article  PubMed  CAS  Google Scholar 

  • 116. Schneider HC, Berthold J, Bauer MF, Dietmeier K, Guiard B, Brunner M, Neupert W (1994) Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature 371:768-774

    Article  PubMed  CAS  Google Scholar 

  • 117. Sesaki H, Southard SM, Hobbs AE, Jensen RE (2003a) Cells lacking Pcp1p/Ugo2p, a rhomboid-like protease required for Mgm1p processing, lose mtDNA and mitochondrial structure in a Dnm1p-dependent manner, but remain competent for mitochondrial fusion. Biochem Biophys Res Commun 308:276-283

    Article  PubMed  CAS  Google Scholar 

  • 118. Sesaki H, Southard SM, Yaffe MP, Jensen RE (2003b) Mgm1p, a dynamin-related GTPase, is essential for fusion of the mitochondrial outer membrane. Mol Biol Cell 14:2342-2356

    Article  PubMed  CAS  Google Scholar 

  • 119. Shah ZH, Hakkaart GAJ, Arku B, DeJong L, Van der Speck H, Grivell L, Jacobs HT (2000) The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p complements a yeast yme1 disruptant. FEBS Lett 478:267-270

    Article  PubMed  CAS  Google Scholar 

  • 120. Shah ZH, Migliosi V, Miller SC, Wang A, Friedman TB, Jacobs HT (1998) Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus. Genomics 48:384-388

    Article  PubMed  CAS  Google Scholar 

  • 121. Shaw JM, Nunnari J (2002) Mitochondrial dynamics and division in budding yeast. Trends Cell Biol 12:178-184

    Article  PubMed  CAS  Google Scholar 

  • 122. Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, Rehling P, Pfanner N, Meisinger C (2003) The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci USA 100:13207-13212

    Article  PubMed  CAS  Google Scholar 

  • 123. Stahlberg H, Kutejova E, Suda K, Wolpensinger B, Lustig A, Schatz G, Engel A, Suzuki CK (1999) Mitochondrial Lon of Saccharomyces cerevisiae is a ring-shaped protease with seven flexible subunits. Proc Natl Acad Sci USA 96:6787-6790

    Article  PubMed  CAS  Google Scholar 

  • 124. Steglich G, Neupert W, Langer T (1999) Prohibitins regulate membrane protein degradation by the m-AAA protease in mitochondria. Mol Cell Biol 19:3435-3442

    PubMed  CAS  Google Scholar 

  • 125. Suzuki CK, Suda K, Wang N, Schatz G (1994) Requirement for the yeast gene LON in intramitochondrial proteolysis and maintenance of respiration. Science 264:273-276

    PubMed  CAS  Google Scholar 

  • 126. Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for induction. J Cell Biol 119:301-311

    Article  PubMed  CAS  Google Scholar 

  • 127. Tatsuta T, Model K, Langer T (2005) Formation of membrane-bound ring complexes by prohibitins in mitochondria. Mol Biol Cell 16:248-259

    Article  PubMed  CAS  Google Scholar 

  • 128. Tauer R, Mannhaupt G, Schnall R, Pajic A, Langer T, Feldmann H (1994) Yta10p, a member of a novel ATPase family in yeast, is essential for mitochondrial function. FEBS Lett 353:197-200

    Article  PubMed  CAS  Google Scholar 

  • 129. Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS (2003) Characterization of the human heart mitochondrial proteome. Nat Biotechnol 21:281-286

    Article  PubMed  CAS  Google Scholar 

  • 130. Teichmann U, van Dyck L, Guiard B, Fischer H, Glockshuber R, Neupert W, Langer T (1996) Substitution of PIM1 protease in mitochondria by Escherichia coli Lon protease. J Biol Chem 271:10137-10142

    Article  PubMed  CAS  Google Scholar 

  • 131. Thorsness PE, Fox TD (1993) Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus. Genetics 134:21-28

    PubMed  CAS  Google Scholar 

  • 132. Thorsness PE, White KH, Fox TD (1993) Inactivation of YME1, a member of the ftsH-SEC18-PAS1-CDC48 family of putative ATPase-encoding genes, causes increased escape of DNA from mitochondria in Saccharomyces cerevisiae. Mol Cell Biol 13:5418-5426

    PubMed  CAS  Google Scholar 

  • 133. Traven A, Wong JM, Xu D, Sopta M, Ingles CJ (2001) Interorganellar communication. Altered nuclear gene expression profiles in a yeast mitochondrial dna mutant. J Biol Chem 276:4020-4027

    Article  PubMed  CAS  Google Scholar 

  • 134. Truscott K, Brandner K, Pfanner N (2003) Mechanisms of protein import into mitochondria. Curr Biol 13:R326-337

    Article  PubMed  CAS  Google Scholar 

  • 135. Tzagoloff A, Yue J, Jang J, Paul MF (1994) A new member of a family of ATPases is essential for assembly of mitochondrial respiratory chain and ATP synthetase complexes in Saccharomyces cerevisiae. J Biol Chem 269:26144-26151

    PubMed  CAS  Google Scholar 

  • 136. Van Dijl JM, Kutejova E, Suda K, Perecko D, Schatz G, Suzuki CK (1998) The ATPase and protease domains of yeast mitochondrial Lon: roles in proteolysis and respiration-dependent growth. Proc Natl Acad Sci USA 95:10584-10589

    Article  Google Scholar 

  • 137. Van Dyck L, Dembowski M, Neupert W, Langer T (1998) Mcx1p, a ClpX homologue in mitochondria of Saccharomyces cerevisiae. FEBS Lett 438:250-254

    Article  Google Scholar 

  • 138. Van Dyck L, Langer T (1999) ATP-dependent proteases controlling mitochondrial function in the yeast Saccharomyces cerevisiae. Cell Mol Life Sci 55:825-842

    Google Scholar 

  • 139. Van Dyck L, Neupert W, Langer T (1998) The ATP-dependent PIM1 protease is required for the expression of intron-containing genes in mitochondria. Genes Dev 12:1515-1524

    Google Scholar 

  • 140. Van Dyck L, Pearce DA, Sherman F (1994) PIM1 encodes a mitochondrial ATP-dependent protease that is required for mitochondrial function in the yeast Saccharomyces cerevisiae. J Biol Chem 269:238-242

    Google Scholar 

  • 141. Voos W, Röttgers K (2002) Molecular chaperones as essential mediators of mitochondrial biogenesis. Biochim Biophys Acta 1592:51-62

    Article  PubMed  CAS  Google Scholar 

  • 142. Wagner I, Arlt H, van Dyck L, Langer T, Neupert W (1994) Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria. EMBO J 13:5135-5145

    PubMed  CAS  Google Scholar 

  • 143. Wagner I, Van Dyck L, Savel'ev A, Neupert W, Langer T (1997) Autocatalytic processing of the ATP-dependent PIM1 protease: Crucial function of a pro-region for sorting to mitochondria. EMBO J 16:7317-7325

    Article  PubMed  CAS  Google Scholar 

  • 144. Wang N, Gottesman S, Willingham MC, Gottesman S, Maurizi MR (1993) A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease. Proc Natl Acad Sci USA 90:11247-11251

    Article  PubMed  CAS  Google Scholar 

  • 145. Watabe S, Kimura T (1985) ATP-dependent protease in bovine adrenal cortex. J Biol Chem 260:5511-5517

    PubMed  CAS  Google Scholar 

  • 146. Weber ER, Hanekamp T, Thorsness PE (1996) Biochemical and functional analysis of the YME1 gene product, an ATP and zinc-dependent mitochondrial protease from S. cerevisiae. Mol Biol Cell 7:307-317

    PubMed  CAS  Google Scholar 

  • 147. Westermann B, Prip-Buus C, Neupert W, Schwarz E (1995) The role of the GrpE homologue, Mge1p, in mediating protein import and protein folding in mitochondria. EMBO J 14:3452-3460

    PubMed  CAS  Google Scholar 

  • 148. Ye Y, Meyer HH, Rapoport TA (2001) The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature 414:652-656

    Article  PubMed  CAS  Google Scholar 

  • 149. Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, Ron D (2004) Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J Cell Sci 117:4055-4066

    Article  PubMed  CAS  Google Scholar 

  • 150. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, Mori K (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol Cell Biol 20:6755-6767

    Article  PubMed  CAS  Google Scholar 

  • 151. Yu RC, Hanson PI, Jahn R, Brünger AT (1998) Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP. Nat Struct Biol 5:803-811

    Article  PubMed  CAS  Google Scholar 

  • 152. Zehnbauer BA, Foley EC, Henderson GW, Markovitz A (1981) Identification and purification of the Lon+ (capR+) gene product, a DNA-binding protein. Proc Natl Acad Sci USA 78:2043-2047

    Article  PubMed  CAS  Google Scholar 

  • 153. Zhang K, Kaufman RJ (2004) Signaling the unfolded protein response from the endoplasmic reticulum. J Biol Chem 279:25935-25938

    Article  PubMed  CAS  Google Scholar 

  • 154. Zhang X, Shaw A, Bates PA, Newman RH, Gowen B, Orlova E, Gorman MA, Kondo H, Dokurno P, Lally J, Leonhard G, Meyer H, Van Heel M, Freemont PS (2000) Structure of the AAA ATPase p97. Mol Cell 6:1473-1484

    Article  PubMed  CAS  Google Scholar 

  • 155. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ (2002) A mitochondrial specific stress response in mammalian cells. EMBO J 21:4411-4419

    Article  PubMed  CAS  Google Scholar 

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  1. Institut für Genetik, Universität Köln, Zülpicher Str. 47, 50674 Köln, Germany

    Mark Nolden, Brigitte Kisters-Woike, Thomas Langer & Martin Graef

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Nolden, M., Kisters-Woike, B., Langer, T., Graef, M. Quality control of proteins in the mitochondrion. In: Braakman, I. (eds) Chaperones. Topics in Current Genetics, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_106

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