Noninvasive diagnostics of mitochondrial disorders in isolated lymphocytes with high resolution respirometry

BBA Clinical

Volumn 2, Issue , 2014, Pages 62-71

  Pecina, Petr ^a   Houšťková, Hana ^b   Mráček, Tomáš ^a   Pecinová, Alena ^a   Nůsková, Hana ^a   Tesařová, Markéta ^c   Hansíková, Hana ^c   Janota, Jan ^b   Zeman, Jiří ^c   Houštěk, Josef ^a  

^a INSTITUTE OF PHYSIOLOGY   (Czech Republic)

^b Thomayer's Teaching Hospital   (Czech Republic)

^c CHARLES UNIVERSITY   (Czech Republic)

Author keywords

Diagnostics; Lymphocytes; Mitochondrial diseases; Oxidative phosphorylation; Respirometry

Indexed keywords

CYTOCHROME C OXIDASE; DIGITONIN; GLYCEROPHOSPHATE; OLIGOMYCIN; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE; UBIQUINOL CYTOCHROME C REDUCTASE; UNCLASSIFIED DRUG;

ADOLESCENT; ADULT; ARTICLE; BREATHING RATE; CHILD; CLINICAL ARTICLE; COMPLEX I DEFICIENCY; COMPLEX V DEFICIENCY; CONTROLLED STUDY; CYTOCHROME C OXIDASE DEFICIENCY; CYTOFLUOROMETRY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FLOW CYTOMETRY; GENE; GENE MUTATION; HUMAN; IMMUNODETECTION; LEIGH DISEASE; LYMPHOCYTE; MITOCHONDRIAL MEMBRANE POTENTIAL; NATIVE POLYACRYLAMIDE GEL ELECTROPHORESIS; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; OXYGEN TENSION; RESPIRATORY CHAIN; RESPIROMETRY; SURF 1 GENE; TMEM70 GENE; WESTERN BLOTTING;

EID: 84907978318     PISSN: 22146474     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbacli.2014.09.003     Document Type: Article

References (56)

1. DiMauro S. Mitochondrial medicine. Biochim. Biophys. Acta 2004, 1659:107-114.
2. DiMauro S. Mitochondrial DNA medicine. Biosci. Rep. 2007, 27:5-9.
3. Vafai S.B., Mootha V.K. Mitochondrial disorders as windows into an ancient organelle. Nature 2012, 491:374-383.
4. Cizkova A., Stranecky V., Mayr J.A., Tesarova M., Havlickova V., Paul J., Ivanek R., Kuss A.W., Hansikova H., Kaplanova V., Vrbacky M., Hartmannova H., Noskova L., Honzik T., Drahota Z., Magner M., Hejzlarova K., Sperl W., Zeman J., Houstek J., Kmoch S. TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. Nat. Genet. 2008, 40:1288-1290.
5. Houstek J., Kmoch S., Zeman J. TMEM70 protein - a novel ancillary factor of mammalian ATP synthase. Biochim. Biophys. Acta 2009, 1787:529-532.
6. Antonicka H., Ostergaard E., Sasarman F., Weraarpachai W., Wibrand F., Pedersen A.M., Rodenburg R.J., van der Knaap M.S., Smeitink J.A., Chrzanowska-Lightowlers Z.M., Shoubridge E.A. Mutations in C12orf65 in patients with encephalomyopathy and a mitochondrial translation defect. Am. J. Hum. Genet. 2010, 87:115-122.
7. Weraarpachai W., Sasarman F., Nishimura T., Antonicka H., Aure K., Rotig A., Lombes A., Shoubridge E.A. Mutations in C12orf62, a factor that couples COX I synthesis with cytochrome c oxidase assembly, cause fatal neonatal lactic acidosis. Am. J. Hum. Genet. 2012, 90:142-151.
8. Sugiana C., Pagliarini D.J., McKenzie M., Kirby D.M., Salemi R., Abu-Amero K.K., Dahl H.H., Hutchison W.M., Vascotto K.A., Smith S.M., Newbold R.F., Christodoulou J., Calvo S., Mootha V.K., Ryan M.T., Thorburn D.R. Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Am. J. Hum. Genet. 2008, 83:468-478.
9. Weraarpachai W., Antonicka H., Sasarman F., Seeger J., Schrank B., Kolesar J.E., Lochmuller H., Chevrette M., Kaufman B.A., Horvath R., Shoubridge E.A. Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nat. Genet. 2009, 41:833-837.
10. Janer A., Antonicka H., Lalonde E., Nishimura T., Sasarman F., Brown G.K., Brown R.M., Majewski J., Shoubridge E.A. An RMND1 mutation causes encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect. Am. J. Hum. Genet. 2012, 91:737-743.
11. Ghezzi D., Goffrini P., Uziel G., Horvath R., Klopstock T., Lochmuller H., D'Adamo P., Gasparini P., Strom T.M., Prokisch H., Invernizzi F., Ferrero I., Zeviani M. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nat. Genet. 2009, 41:654-656.
12. Hao H.X., Khalimonchuk O., Schraders M., Dephoure N., Bayley J.P., Kunst H., Devilee P., Cremers C.W., Schiffman J.D., Bentz B.G., Gygi S.P., Winge D.R., Kremer H., Rutter J. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 2009, 325:1139-1142.
13. Pagliarini D.J., Calvo S.E., Chang B., Sheth S.A., Vafai S.B., Ong S.E., Walford G.A., Sugiana C., Boneh A., Chen W.K., Hill D.E., Vidal M., Evans J.G., Thorburn D.R., Carr S.A., Mootha V.K. A mitochondrial protein compendium elucidates complex I disease biology. Cell 2008, 134:112-123.
14. Bohm M., Pronicka E., Karczmarewicz E., Pronicki M., Piekutowska-Abramczuk D., Sykut-Cegielska J., Mierzewska H., Hansikova H., Vesela K., Tesarova M., Houstkova H., Houstek J., Zeman J. Retrospective, multicentric study of 180 children with cytochrome C oxidase deficiency. Pediatr. Res. 2006, 59:21-26.
15. Rotig A., Cormier V., Blanche S., Bonnefont J.P., Ledeist F., Romero N., Schmitz J., Rustin P., Fischer A., Saudubray J.M., et al. Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J. Clin. Invest. 1990, 86:1601-1608.
16. Cormier V., Rotig A., Tardieu M., Colonna M., Saudubray J.M., Munnich A. Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalomyopathy. Am. J. Hum. Genet. 1991, 48:643-648.
17. Burgeois M., Goutieres F., Chretien D., Rustin P., Munnich A., Aicardi J. Deficiency in complex II of the respiratory chain, presenting as a leukodystrophy in two sisters with Leigh syndrome. Brain Dev. 1992, 14:404-408.
18. Tatuch Y., Robinson B.H. The mitochondrial DNA mutation at 8993 associated with NARP slows the rate of ATP synthesis in isolated lymphoblast mitochondria. Biochem. Biophys. Res. Commun. 1993, 192:124-128.
19. Rustin P., Chretien D., Bourgeron T., Gerard B., Rotig A., Saudubray J.M., Munnich A. Biochemical and molecular investigations in respiratory chain deficiencies. Clin. Chim. Acta 1994, 228:35-51.
20. Chretien D., Rustin P., Bourgeron T., Rotig A., Saudubray J.M., Munnich A. Reference charts for respiratory chain activities in human tissues. Clin. Chim. Acta 1994, 228:53-70.
21. Uziel G., Moroni I., Lamantea E., Fratta G.M., Ciceri E., Carrara F., Zeviani M. Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families. J. Neurol. Neurosurg. Psychiatry 1997, 63:16-22.
22. Artuch R., Colome C., Playan A., Alcaine M.J., Briones P., Montoya J., Vilaseca M.A., Pineda M. Oxygen consumption measurement in lymphocytes for the diagnosis of pediatric patients with oxidative phosphorylation diseases. Clin. Biochem. 2000, 33:481-485.
23. Brown M.D., Trounce I.A., Jun A.S., Allen J.C., Wallace D.C. Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber's hereditary optic neuropathy mitochondrial DNA mutation. J. Biol. Chem. 2000, 275:39831-39836.
24. Capkova M., Hansikova H., Godinot C., Houst'kova H., Houstek J., Zeman J. A new missense mutation of 574C>T in the SURF1 gene-biochemical and molecular genetic study in seven children with Leigh syndrome. Cas. Lek. Cesk. 2002, 141:636-641.
25. Chretien D., Benit P., Chol M., Lebon S., Rotig A., Munnich A., Rustin P. Assay of mitochondrial respiratory chain complex I in human lymphocytes and cultured skin fibroblasts. Biochem. Biophys. Res. Commun. 2003, 301:222-224.
26. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72:248-254.
27. Pecina P., Capkova M., Chowdhury S.K., Drahota Z., Dubot A., Vojtiskova A., Hansikova H., Houst'kova H., Zeman J., Godinot C., Houstek J. Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome. Biochim. Biophys. Acta 2003, 1639:53-63.
28. Pecina P., Gnaiger E., Zeman J., Pronicka E., Houstek J. Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations. Am. J. Physiol. Cell Physiol. 2004, 287:C1384-C1388.
29. Gnaiger E., Steinlechner-Maran R., Mendez G., Eberl T., Margreiter R. Control of mitochondrial and cellular respiration by oxygen. J. Bioenerg. Biomembr. 1995, 27:583-596.
30. Schagger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100kDa. Anal. Biochem. 1987, 166:368-379.
31. Wittig I., Braun H.P., Schagger H. Blue native PAGE. Nat. Protoc. 2006, 1:418-428.
32. Floryk D., Houstek J. Tetramethyl rhodamine methyl ester (TMRM) is suitable for cytofluorometric measurements of mitochondrial membrane potential in cells treated with digitonin. Biosci. Rep. 1999, 19:27-34.
33. Tiranti V., Hoertnagel K., Carrozzo R., Galimberti C., Munaro M., Granatiero M., Zelante L., Gasparini P., Marzella R., Rocchi M., Bayona-Bafaluy M.P., Enriquez J.A., Uziel G., Bertini E., Dionisi-Vici C., Franco B., Meitinger T., Zeviani M. Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am. J. Hum. Genet. 1998, 63:1609-1621.
34. Zhu Z., Yao J., Johns T., Fu K., De Bie I., Macmillan C., Cuthbert A.P., Newbold R.F., Wang J., Chevrette M., Brown G.K., Brown R.M., Shoubridge E.A. SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nat. Genet. 1998, 20:337-343.
35. Kovarova N., Cizkova Vrbacka A., Pecina P., Stranecky V., Pronicka E., Kmoch S., Houstek J. Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency caused by SURF1 gene mutations. Biochim. Biophys. Acta 2012, 1822:1114-1124.
36. Gnaiger E., Lassnig B., Kuznetsov A., Rieger G., Margreiter R. Mitochondrial oxygen affinity, respiratory flux control and excess capacity of cytochrome c oxidase. J. Exp. Biol. 1998, 201:1129-1139.
37. Honzik T., Tesarova M., Mayr J.A., Hansikova H., Jesina P., Bodamer O., Koch J., Magner M., Freisinger P., Huemer M., Kostkova O., van Coster R., Kmoch S., Houstek J., Sperl W., Zeman J. Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation. Arch. Dis. Child. 2010, 95:296-301.
38. Mazat J.P., Rossignol R., Malgat M., Rocher C., Faustin B., Letellier T. What do mitochondrial diseases teach us about normal mitochondrial functions. . .that we already knew: threshold expression of mitochondrial defects. Biochim. Biophys. Acta 2001, 1504:20-30.
39. Rossignol R., Faustin B., Rocher C., Malgat M., Mazat J.P., Letellier T. Mitochondrial threshold effects. Biochem. J. 2003, 370:751-762.
40. Mracek T., Drahota Z., Houstek J. The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues. Biochim. Biophys. Acta 2013, 1827:401-410.
41. Jaksch M., Ogilvie I., Yao J., Kortenhaus G., Bresser H.G., Gerbitz K.D., Shoubridge E.A. Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. Hum. Mol. Genet. 2000, 9:795-801.
42. Vesela K., Hansikova H., Tesarova M., Martasek P., Elleder M., Houstek J., Zeman J. Clinical, biochemical and molecular analyses of six patients with isolated cytochrome c oxidase deficiency due to mutations in the SCO2 gene. Acta Paediatr. 2004, 93:1312-1317.
43. Hejzlarova K., Mracek T., Vrbacky M., Kaplanova V., Karbanova V., Nuskova H., Pecina P., Houstek J. Nuclear genetic defects of mitochondrial ATP synthase. Physiol. Res. 2014, 63(Suppl. 1):S57-S71.
44. Larsson N.G., Tulinius M.H., Holme E., Oldfors A., Andersen O., Wahlstrom J., Aasly J. Segregation and manifestations of the mtDNA tRNA(Lys) A→G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. Am. J. Hum. Genet. 1992, 51:1201-1212.
45. Holme E., Larsson N.G., Oldfors A., Tulinius M., Sahlin P., Stenman G. Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A→G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. Am. J. Hum. Genet. 1993, 52:551-556.
46. Tulinius M.H., Houshmand M., Larsson N.G., Holme E., Oldfors A., Holmberg E., Wahlstrom J. De novo mutation in the mitochondrial ATP synthase subunit 6 gene (T8993G) with rapid segregation resulting in Leigh syndrome in the offspring. Hum. Genet. 1995, 96:290-294.
47. Houshmand M., Lindberg C., Moslemi A.R., Oldfors A., Holme E. A novel heteroplasmic point mutation in the mitochondrial tRNA(Lys) gene in a sporadic case of mitochondrial encephalomyopathy: de novo mutation and no transmission to the offspring. Hum. Mutat. 1999, 13:203-209.
48. Lamantea E., Carrara F., Mariotti C., Morandi L., Tiranti V., Zeviani M. A novel nonsense mutation (Q352X) in the mitochondrial cytochrome b gene associated with a combined deficiency of complexes I and III. Neuromuscul. Disord. 2002, 12:49-52.
49. Leo-Kottler B., Luberichs J., Besch D., Christ-Adler M., Fauser S. Leber's hereditary optic neuropathy: clinical and molecular genetic results in a patient with a point mutation at np T11253C (isoleucine to threonine) in the ND4 gene and spontaneous recovery. Graefes Arch. Clin. Exp. Ophthalmol. 2002, 240:758-764.
50. Chacko B.K., Kramer P.A., Ravi S., Johnson M.S., Hardy R.W., Ballinger S.W., Darley-Usmar V.M. Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood. Lab. Invest 2013, 93:690-700.
51. Widlansky M.E., Wang J., Shenouda S.M., Hagen T.M., Smith A.R., Kizhakekuttu T.J., Kluge M.A., Weihrauch D., Gutterman D.D., Vita J.A. Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes. Transl. Res. 2010, 156:15-25.
52. Japiassu A.M., Santiago A.P., d'Avila J.C., Garcia-Souza L.F., Galina A., Castro Faria-Neto H.C., Bozza F.A., Oliveira M.F. Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5'-triphosphate synthase activity. Crit. Care Med. 2011, 39:1056-1063.
53. Leuner K., Schulz K., Schutt T., Pantel J., Prvulovic D., Rhein V., Savaskan E., Czech C., Eckert A., Muller W.E. Peripheral mitochondrial dysfunction in Alzheimer's disease: focus on lymphocytes. Mol. Neurobiol. 2012, 46:194-204.
54. Tyurina Y.Y., Winnica D.E., Kapralova V.I., Kapralov A.A., Tyurin V.A., Kagan V.E. LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: implications for mitochondrial dysfunction associated with Parkinson's disease. Mol. Nutr. Food Res. 2013, 57:1410-1422.
55. Lee S., Sheck L., Crowston J.G., Van Bergen N.J., O'Neill E.C., O'Hare F., Kong Y.X., Chrysostomou V., Vincent A.L., Trounce I.A. Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts. Invest. Ophthalmol. Vis. Sci. 2012, 53:2431-2437.
56. Cordero M.D., De Miguel M., Moreno Fernandez A.M., Carmona Lopez I.M., Garrido Maraver J., Cotan D., Gomez Izquierdo L., Bonal P., Campa F., Bullon P., Navas P., Sanchez Alcazar J.A. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease. Arthritis Res. Ther. 2010, 12:R17.