Introducing the human Leigh syndrome mutation T9176G into Saccharomyces cerevisiae mitochondrial DNA leads to severe defects in the incorporation of Atp6p into the ATP synthase and in the mitochondrial morphology

Human Molecular Genetics

Volumn 18, Issue 15, 2009, Pages 2889-2898

  Kucharczyk, Roza ^a   Salin, Bénédicte ^a   Di Rago, J P ^a  

^a Institut de Biochimie et Genetique Cellulaires   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE 6 PROTEIN; ARGININE; LEUCINE; MITOCHONDRIAL DNA; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; UNCLASSIFIED DRUG;

ALPHA HELIX; AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENERGY METABOLISM; GENE MUTATION; LEIGH DISEASE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PATHOGENICITY; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE;

SACCHAROMYCES CEREVISIAE;

CELL LINE; HUMANS; LEIGH DISEASE; MITOCHONDRIA; MITOCHONDRIAL PROTON-TRANSLOCATING ATPASES; MUTATION, MISSENSE; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS;

EID: 67650964198     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp226     Document Type: Article

References (63)

1. Saraste, M. (1999) Oxidative phosphorylation at the fin de siecle. Science, 283, 1488-1493.
2. Schon, E.A., Santra, S., Pallotti, F. and Girvin, M.E. (2001) Pathogenesis of primary defects in mitochondrial ATP synthesis. Semin. Cell Dev. Biol., 12, 441-448.
3. Houstek, J., Pickova, A., Vojtiskova, A., Mracek, T., Pecina, P. and Jesina, P. (2006) Mitochondrial diseases and genetic defects of ATP synthase. Biochim. Biophys. Acta, 1757, 1400-1405.
4. Kucharczyk, R., Zick, M., Bietenhader, M., Rak, M., Couplan, E., Blondel, M., Caubet, S.D. and di Rago, J.P. (2009) Mitochondrial ATP synthase disorders: Molecular mechanisms and the quest for curative therapeutic approaches. Biochim. Biophys. Acta, 1793, 186-199.
5. Fillingame, R.H., Angevine, C.M. and Dmitriev, O.Y. (2003) Mechanics of coupling proton movements to c-ring rotation in ATP synthase. FEBS Lett., 555, 29-34.
6. Carrozzo, R., Tessa, A., Vazquez-Memije, M.E., Piemonte, F., Patrono, C., Malandrini, A., Dionisi-Vici, C., Vilarinho, L., Villanova, M., Schagger, H. et al. (2001) The T9176G mtDNA mutation severely affects ATP production and results in Leigh syndrome. Neurology, 56, 687-690.
7. Akagi, M., Inui, K., Tsukamoto, H., Sakai, N., Muramatsu, T., Yamada, M., Matsuzaki, K., Goto, Y., Nonaka, I. and Okada, S. (2002) A point mutation of mitochondrial ATPase 6 gene in Leigh syndrome. Neuromuscul. Disord., 12, 53-55.
8. Carrozzo, R., Rizza, T., Lucioli, S., Pierini, R., Bertini, E. and Santorelli, F.M. (2004) A mitochondrial ATPase 6 mutation is associated with Leigh syndrome in a family and affects proton flow and adenosine triphosphate output when modeled in Escherichia coli. Acta Paediatr. Suppl., 93, 65-67.
9. Contamine, V. and Picard, M. (2000) Maintenance and integrity of the mitochondrial genome: A plethora of nuclear genes in the budding yeast. Microbiol. Mol. Biol. Rev., 64, 281-315.
10. Rak, M., Tetaud, E., Godard, F., Sagot, I., Salin, B., Duvezin-Caubet, S., Slonimski, P.P., Rytka, J. and di Rago, J.P. (2007) Yeast cells lacking the mitochondrial gene encoding the ATP synthase subunit 6 exhibit a selective loss of complex IV and unusual mitochondrial morphology. J. Biol. Chem., 282, 10853-10864.
11. Schagger, H. and Pfeiffer, K. (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J., 19, 1777-1783.
12. Emaus, R.K., Grunwald, R. and Lemasters, J.J. (1986) Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties. Biochim. Biophys. Acta, 850 436-448.
13. Venard, R., Brethes, D., Giraud, M.F., Vaillier, J., Velours, J. and Haraux, F. (2003) Investigation of the role and mechanism of IF1 and STF1 proteins, twin inhibitory peptides which interact with the yeast mitochondrial ATP synthase. Biochemistry, 42, 7626-7636.
14. Zeng, X., Kucharczyk, R., di Rago, J.P. and Tzagoloff, A. (2007) The leader peptide of yeast Atp6p is required for efficient interaction with the Atp9p ring of the mitochondrial ATPase. J. Biol. Chem., 282 36167-36176.
15. Michon, T., Galante, M. and Velours, J. (1988) NH2-terminal sequence of the isolated yeast ATP synthase subunit 6 reveals post-translational cleavage. Eur. J. Biochem., 172, 621-625.
16. Zeng, X., Neupert, W. and Tzagoloff, A. (2007) The metalloprotease encoded by ATP23 has a dual function in processing and assembly of subunit 6 of mitochondrial ATPase. Mol. Biol. Cell, 18, 617-626.
17. Holt, I.J., Harding, A.E., Petty, R.K. and Morgan-Hughes, J.A. (1990) A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am. J. Hum. Genet., 46, 428-433.
18. Rak, M., Tetaud, E., Duvezin-Caubet, S., Ezkurdia, N., Bietenhader, M., Rytka, J. and di Rago, J.P. (2007) A yeast model of the neurogenic ataxia retinitis pigmentosa (NARP) T8993G mutation in the mitochondrial ATP synthase-6 gene. J. Biol. Chem., 282, 34039-34047.
19. Goyon, V., Fronzes, R., Salin, B., di-Rago, J.P., Velours, J. and Brethes, D. (2008) Yeast cells depleted in Atp14p fail to assemble Atp6p within the ATP synthase and exhibit altered mitochondrial cristae morphology. J. Biol. Chem., 283, 9749-9758.
20. Paumard, P., Vaillier, J., Coulary, B., Schaeffer, J., Soubannier, V., Mueller, D.M., Brethes, D., di Rago, J.P. and Velours, J. (2002) The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J., 21, 221-230.
21. Lefebvre-Legendre, L., Salin, B., Schaeffer, J., Brethes, D., Dautant, A., Ackerman, S.H. and di Rago, J.P. (2005) Failure to assemble the alpha 3 beta 3 subcomplex of the ATP synthase leads to accumulation of the alpha and beta subunits within inclusion bodies and the loss of mitochondrial cristae in Saccharomyces cerevisiae. J. Biol. Chem., 280, 18386-18392.
22. Weimann, T., Vaillier, J., Salin, B. and Velours, J. (2008) The intermembrane space loop of subunit b (4) is a major determinant of the stability of yeast oligomeric ATP synthases. Biochemistry, 47 3556-3563.
23. Bustos, D.M. and Velours, J. (2005) The modification of the conserved GXXXG motif of the membrane-spanning segment of subunit g destabilizes the supramolecular species of yeast ATP synthase. J. Biol. Chem., 280, 29004-29010.
24. Arselin, G., Vaillier, J., Salin, B., Schaeffer, J., Giraud, M.F., Dautant, A., Brethes, D. and Velours, J. (2004) The modulation in subunits e and g amounts of yeast ATP synthase modifies mitochondrial cristae morphology. J. Biol. Chem., 279, 40392-40399.
25. Giraud, M.F., Paumard, P., Soubannier, V., Vaillier, J., Arselin, G., Salin, B., Schaeffer, J., Brethes, D., di Rago, J.P. and Velours, J. (2002) Is there a relationship between the supramolecular organization of the mitochondrial ATP synthase and the formation of cristae? Biochim. Biophys. Acta, 1555, 174-180.
26. Soubannier, V., Vaillier, J., Paumard, P., Coulary, B., Schaeffer, J. and Velours, J. (2002) In the absence of the first membrane-spanning segment of subunit 4(b), the yeast ATP synthase is functional but does not dimerize or oligomerize. J. Biol. Chem., 277, 10739-10745.
27. Allen, R.D. (1995) Membrane tubulation and proton pumps. Protoplasma 189, 1-8.
28. Allen, R.D., Schroeder, C.C. and Fok, A.K. (1989) An investigation of mitochondrial inner membranes by rapid-freeze deep-etch techniques. J. Cell Biol., 108, 2233-2240.
29. Frey, T.G., Renken, C.W. and Perkins, G.A. (2002) Insight into mitochondrial structure and function from electron tomography. Biochim. Biophys. Acta, 1555, 196-203.
30. Gilkerson, R.W., Selker, J.M. and Capaldi, R.A. (2003) The cristal membrane of mitochondria is the principal site of oxidative phosphorylation. FEBS Lett., 546, 355-358.
31. Carrozzo, R., Murray, J., Capuano, O., Tessa, A., Chichierchia, G., Neglia, M.R., Capaldi, R.A. and Santorelli, F.M. (2000) A novel mtDNA mutation in the ATPase6 gene studied by E. coli modeling. Neurol. Sci., 21, S983-S984.
32. Moore, K.J. and Fillingame, R.H. (2008) Structural interactions between transmembrane helices 4 and 5 of subunit a and the subunit c ring of Escherichia coli ATP synthase. J. Biol. Chem., 283, 31726-31735.
33. Bonnefoy, N. and Fox, T.D. (2001) Genetic transformation of Saccharomyces cerevisiae mitochondria. Methods Cell Biol., 65, 381-396.
34. Ackerman, S.H. and Tzagoloff, A. (2007) Methods to determine the status of mitochondrial ATP synthase assembly. Methods Mol. Biol., 372 363-377.
35. Velours, J. and Arselin, G. (2000) The Saccharomyces cerevisiae ATP synthase. J. Bioenerg. Biomembr., 32, 383-390.
36. Ackerman, S.H. and Tzagoloff, A. (2005) Function, structure, and biogenesis of mitochondrial ATP synthase. Prog. Nucleic Acid Res. Mol. Biol., 80, 95-133.
37. Rak, M., Zeng, X., Briere, J.J. and Tzagoloff, A. (2009) Assembly of F0 in Saccharomyces cerevisiae. Biochim. Biophys. Acta, 1793, 108-116.
38. Hadikusumo, R.G., Meltzer, S., Choo, W.M., Jean-Francois, M.J., Linnane, A.W. and Marzuki, S. (1988) The definition of mitochondrial H+ ATPase assembly defects in mit- mutants of Saccharomyces cerevisiae with a monoclonal antibody to the enzyme complex as an assembly probe. Biochim. Biophys. Acta, 933, 212-222.
39. Tzagoloff, A., Barrientos, A., Neupert, W. and Herrmann, J.M. (2004) Atp10p assists assembly of Atp6p into the F0 unit of the yeast mitochondrial ATPase. J. Biol. Chem., 279, 19775-19780.
40. Hermolin, J. and Fillingame, R.H. (1995) Assembly of F0 sector of Escherichia coli H+ ATP synthase. Interdependence of subunit insertion into the membrane. J. Biol. Chem., 270, 2815-2817.
41. Paul, M.F., Barrientos, A. and Tzagoloff, A. (2000) A single amino acid change in subunit 6 of the yeast mitochondrial ATPase suppresses a null mutation in ATP10. J. Biol. Chem., 275, 29238-29243.
42. Lefebvre-Legendre, L., Vaillier, J., Benabdelhak, H., Velours, J., Slonimski, P.P. and di Rago, J.P. (2001) Identification of a nuclear gene (FMC1) required for the assembly/stability of yeast mitochondrial F(1)-ATPase in heat stress conditions. J. Biol. Chem., 276, 6789-6796.
43. Carrozzo, R., Murray, J., Santorelli, F.M. and Capaldi, R.A. (2000) The T9176G mutation of human mtDNA gives a fully assembled but inactive ATP synthase when modeled in Escherichia coli. FEBS Lett., 486, 297-299.
44. Carrozzo, R., Wittig, I., Santorelli, F.M., Bertini, E., Hofmann, S., Brandt, U. and Schagger, H. (2006) Subcomplexes of human ATP synthase mark mitochondrial biosynthesis disorders. Ann. Neurol., 59, 265-275.
45. Baracca, A., Barogi, S., Carelli, V., Lenaz, G. and Solaini, G. (2000) Catalytic activities of mitochondrial ATP synthase in patients with mitochondrial DNA T8993G mutation in the ATPase 6 gene encoding subunit a. J. Biol. Chem., 275, 4177-4182.
46. Houstek, J., Klement, P., Hermanska, J., Houstkova, H., Hansikova, H., Van den Bogert, C. and Zeman, J. (1995) Altered properties of mitochondrial ATP-synthase in patients with a T->G mutation in the ATPase 6 (subunit a) gene at position 8993 of mtDNA. Biochim. Biophys. Acta, 1271, 349-357.
47. Manfredi, G., Gupta, N., Vazquez-Memije, M.E., Sadlock, J.E., Spinazzola, A., De Vivo, D.C. and Schon, E.A. (1999) Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene. J. Biol. Chem., 274, 9386-9391.
48. Garcia, J.J., Ogilvie, I., Robinson, B.H. and Capaldi, R.A. (2000) Structure, functioning, and assembly of the ATP synthase in cells from patients with the T8993G mitochondrial DNA mutation. Comparison with the enzyme in Rho(0) cells completely lacking mtDNA. J. Biol. Chem., 275, 11075-11081.
49. Cortes-Hernandez, P., Vazquez-Memije, M.E. and Garcia, J.J. (2007) ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization. J. Biol. Chem., 282, 1051-1058.
50. Kucharczyk, R., Rak, M. and di Rago, P. (2009) Biochemical consequences in yeast of the human mitochondrial DNA 8993T>C mutation in the ATPase6 gene found in NARP/MILS patients. Biochim. Biophys. Acta, 1793 817-824.
51. Lefebvre-Legendre, L., Balguerie, A., Duvezin-Caubet, S., Giraud, M.F., Slonimski, P.P. and Di Rago, J.P. (2003) F1-catalysed ATP hydrolysis is required for mitochondrial biogenesis in Saccharomyces cerevisiae growing under conditions where it cannot respire. Mol. Microbiol., 47, 1329-1339.
52. Cizkova, A., Stranecky, V., Mayr, J.A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A.W., Hansikova, H., Kaplanova, V. et al. (2008) TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. Nat. Genet., 40 1288-1290.
53. Kadenbach, B. (2003) Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim. Biophys. Acta, 1604, 77-94.
54. McBride, H.M., Neuspiel, M. and Wasiak, S. (2006) Mitochondria: More than just a powerhouse. Curr. Biol., 16, R551-R560.
55. Chan, D.C. (2006) Mitochondria: Dynamic organelles in disease, aging, and development. Cell, 125, 1241-1252.
56. Delettre, C., Lenaers, G., Griffoin, J.M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E. et al. (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet., 26, 207-210.
57. Zuchner, S., Mersiyanova, I.V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E.L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J. et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 36, 449-451.
58. Waterham, H.R., Koster, J., van Roermund, C.W., Mooyer, P.A., Wanders, R.J. and Leonard, J.V. (2007) A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med., 356, 1736-1741.
59. Duvezin-Caubet, S., Jagasia, R., Wagener, J., Hofmann, S., Trifunovic, A., Hansson, A., Chomyn, A., Bauer, M.F., Attardi, G., Larsson, N.G. et al. (2006) Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J. Biol. Chem., 281, 37972-37979.
60. Strauss, M., Hofhaus, G., Schröder, R.R. and Kühlbrandt, W. (2008) Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J., 27, 1154-1160.
61. Zick, M., Rabl, R. and Reichert, A.S. (2009) Cristae formation-linking ultrastructure and function of mitochondria. Biochim. Biophys. Acta 1793, 5-19.
62. Meeusen, S., McCaffery, J.M. and Nunnari, J. (2004) Mitochondrial fusion intermediates revealed in vitro. Science, 305, 1747-1752.
63. Steele, D.F., Butler, C.A. and Fox, T.D. (1996) Expression of a recoded nuclear gene inserted into yeast mitochondrial DNA is limited by mRNA-specific translational activation. Proc. Natl Acad. Sci. USA, 93, 5253-5257.