Proteomic and metabolomic analyses of mitochondrial complex I-deficient mouse model generated by spontaneous B2 short interspersed nuclear element (SINE) insertion into NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) gene

Journal of Biological Chemistry

Volumn 287, Issue 24, 2012, Pages 20652-20663

  Leong, Dillon W ^a   Komen, Jasper C ^b   Hewitt, Chelsee A ^a   Arnaud, Estelle ^c   McKenzie, Matthew ^d   Phipson, Belinda ^a   Bahlo, Melanie ^a,e   Laskowski, Adrienne ^b   Kinkel, Sarah A ^a,e   Davey, Gayle M ^e   Heath, William R ^e   Voss, Anne K ^a,e   Zahedi, René P ^f   Pitt, James J ^b   Chrast, Roman ^c   Sickmann, Albert ^f,g   Ryan, Michael T ^h   Smyth, Gordon K ^a,e   Thorburn, David R ^b   Scott, Hamish S ^a,e,i,j  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b ROYAL CHILDREN'S HOSPITAL   (Australia)

^c UNIVERSITY OF LAUSANNE   (Switzerland)

^d HUDSON INSTITUTE OF MEDICAL RESEARCH   (Australia)

^e UNIVERSITY OF MELBOURNE   (Australia)

^f LEIBNIZ INSTITUT FÜR ANALYTISCHE WISSENSCHAFTEN ISAS E V   (Germany)

^g RUHR UNIVERSITY BOCHUM   (Germany)

^h LA TROBE UNIVERSITY   (Australia)

ⁱ CENTRE FOR CANCER BIOLOGY   (Australia)

^j UNIVERSITY OF ADELAIDE   (Australia)

more..

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEX NETWORKS; DEFECTS; FATTY ACIDS; GENES; MAMMALS; MASS SPECTROMETRY; MITOCHONDRIA; NEURODEGENERATIVE DISEASES; PHOSPHORYLATION; PROTEINS;

ABERRANT TRANSCRIPT; EXPRESSION ANALYSIS; METABOLOMIC ANALYSIS; MITOCHONDRIAL COMPLEX; NADH DEHYDROGENASE; OXIDATIVE PHOSPHORYLATION; TANDEM MASS SPECTROMETRY; TRANSPOSABLE ELEMENTS;

IRON COMPOUNDS;

REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE;

ANIMAL EXPERIMENT; ARTICLE; BINDING SITE; CONTROLLED STUDY; FATTY ACID OXIDATION; FEMALE; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC LINKAGE; HOMOZYGOSITY; MALE; METABOLOMICS; MITOCHONDRION; MOUSE; NDUFS4 GENE; NEUROLOGIC DISEASE; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN SYNTHESIS; PROTEOMICS; SINGLE NUCLEOTIDE POLYMORPHISM; TANDEM MASS SPECTROMETRY; TRANSPOSON;

EUKARYOTA; MAMMALIA; MUS;

EID: 84862001736     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.327601     Document Type: Article

References (70)

1. Smeitink, J. A., Zeviani, M., Turnbull, D. M., and Jacobs, H. T. (2006) Mitochondrial medicine. A metabolic perspective on the pathology of oxidative phosphorylation disorders. Cell Metab. 3, 9-13
2. Skladal, D., Halliday, J., and Thorburn, D. R. (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126, 1905-1912 (Pubitemid 36917349)
3. Tucker, E. J., Compton, A. G., Calvo, S. E., and Thorburn, D. R. (2011) The molecular basis of human complex I deficiency. IUBMB Life 63, 669-777
4. Rahman, S., Blok, R. B., Dahl, H. H., Danks, D. M., Kirby, D. M., Chow, C. W., Christodoulou, J., and Thorburn, D. R. (1996) Leigh syndrome. Clinical features and biochemical and DNA abnormalities. Ann. Neurol. 39, 343-351 (Pubitemid 26100758)
5. Kirby, D. M., Crawford, M., Cleary, M. A., Dahl, H. H., Dennett, X., and Thorburn, D. R. (1999) Respiratory chain complex I deficiency. An under-diagnosed energy generation disorder. Neurology 52, 1255-1264 (Pubitemid 29177931)
6. Chinnery, P., Majamaa, K., Turnbull, D., and Thorburn, D. (2006) Treatment for mitochondrial disorders. Cochrane Database Syst. Rev. CD004426
7. Klein, J. A., Longo-Guess, C. M., Rossmann, M. P., Seburn, K. L., Hurd, R. E., Frankel, W. N., Bronson, R. T., and Ackerman, S. L. (2002) The harlequin mouse mutation down-regulates apoptosis-inducing factor. Nature 419, 367-374
8. Joza, N., Oudit, G. Y., Brown, D., Bénit, P., Kassiri, Z., Vahsen, N., Benoit, L., Patel, M. M., Nowikovsky, K., Vassault, A., Backx, P. H., Wada, T., Kroemer, G., Rustin, P., and Penninger, J. M. (2005) Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol. Cell Biol. 25, 10261-10272 (Pubitemid 41681953)
9. Pospisilik, J. A., Knauf, C., Joza, N., Benit, P., Orthofer, M., Cani, P. D., Ebersberger, I., Nakashima, T., Sarao, R., Neely, G., Esterbauer, H., Kozlov, A., Kahn, C. R., Kroemer, G., Rustin, P., Burcelin, R., and Penninger, J. M. (2007) Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 131, 476-491 (Pubitemid 350017761)
10. Ishimura, R., Martin, G. R., and Ackerman, S. L. (2008) Loss of apoptosis-inducing factor results in cell type-specific neurogenesis defects. J. Neurosci. 28, 4938-4948
11. Ghezzi, D., Sevrioukova, I., Invernizzi, F., Lamperti, C., Mora, M., D'Adamo, P., Novara, F., Zuffardi, O., Uziel, G., and Zeviani, M. (2010) Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am. J. Hum. Genet. 86, 639-649
12. Ingraham, C. A., Burwell, L. S., Skalska, J., Brookes, P. S., Howell, R. L., Sheu, S. S., and Pinkert, C. A. (2009) NDUFS4. Creation of a mouse model mimicking a complex I disorder. Mitochondrion 9, 204-210
13. Kruse, S. E., Watt, W. C., Marcinek, D. J., Kapur, R. P., Schenkman, K. A., and Palmiter, R. D. (2008) Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy. Cell Metab. 7, 312-320 (Pubitemid 351455216)
14. Quintana, A., Kruse, S. E., Kapur, R. P., Sanz, E., and Palmiter, R. D. (2010) Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome. Proc. Natl. Acad. Sci. U.S.A. 107, 10996-11001
15. Phipson, B., and Smyth, G. K. (2010) Permutation P-values should never be zero. Calculating exact P-values when permutations are randomly drawn. Stat. Appl. Genet. Mol. Biol. 9, Article 39
16. Irizarry, R. A., Hobbs, B., Collin, F., Beazer-Barclay, Y. D., Antonellis, K. J., Scherf, U., and Speed, T. P. (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4, 249-264
17. Smyth, G. K. (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, Article 3
18. Dai, M., Wang, P., Boyd, A. D., Kostov, G., Athey, B., Jones, E. G., Bunney, W. E., Myers, R. M., Speed, T. P., Akil, H., Watson, S. J., and Meng, F. (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res. 33, e175
19. Wu, D., Lim, E., Vaillant, F., Asselin-Labat, M. L., Visvader, J. E., and Smyth, G. K. (2010) ROAST. Rotation gene set tests for complex microarray experiments. Bioinformatics 26, 2176-2182
20. Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., and Mesirov, J. P. (2005) Gene set enrichment analysis. A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U.S.A. 102, 15545-15550 (Pubitemid 41528093)
21. McKenzie, M., Lazarou, M., Thorburn, D. R., and Ryan, M. T. (2006) Mitochondrial respiratory chain supercomplexes are destabilized in Barth syndrome patients. J. Mol. Biol. 361, 462-469 (Pubitemid 44118343)
22. McKenzie, M., Lazarou, M., Thorburn, D. R., and Ryan, M. T. (2007) Analysis of mitochondrial subunit assembly into respiratory chain complexes using blue native polyacrylamide gel electrophoresis. Anal. Biochem. 364, 128-137 (Pubitemid 46559922)
23. Johnston, A. J., Hoogenraad, J., Dougan, D. A., Truscott, K. N., Yano, M., Mori, M., Hoogenraad, N. J., and Ryan, M. T. (2002) Insertion and assembly of human tom7 into the preprotein translocase complex of the outer mitochondrial membrane. J. Biol. Chem. 277, 42197-42204 (Pubitemid 35257538)
24. Winkler, C., Denker, K., Wortelkamp, S., and Sickmann, A. (2007) Silver-and Coomassie-staining protocols. Detection limits and compatibility with ESI MS. Electrophoresis 28, 2095-2099 (Pubitemid 47040414)
25. Pallotti, F., and Lenaz, G. (2001) Isolation and subfractionation of mitochondria from animal cells and tissue culture lines. Methods Cell Biol. 65, 1-35
26. Sims, N. R., and Anderson, M. F. (2008) Isolation of mitochondria from rat brain using Percoll density gradient centrifugation. Nat. Protoc. 3, 1228-1239
27. Wanders, R. J., Ruiter, J. P., and Wijburg, F. A. (1993) Studies on mitochondrial oxidative phosphorylation in permeabilized human skin fibroblasts. Application to mitochondrial encephalomyopathies. Biochim. Biophys. Acta 1181, 219-222 (Pubitemid 23177211)
28. Rashed, M. S., Bucknall, M. P., Little, D., Awad, A., Jacob, M., Alamoudi, M., Alwattar, M., and Ozand, P. T. (1997) Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. Clin. Chem. 43, 1129-1141 (Pubitemid 27297255)
29. van Vlies, N., Tian, L., Overmars, H., Bootsma, A. H., Kulik, W., Wanders, R. J., Wood, P. A., and Vaz, F. M. (2005) Characterization of carnitine and fatty acid metabolism in the long-chain acyl-CoA dehydrogenase-deficient mouse. Biochem. J. 387, 185-193 (Pubitemid 40524088)
30. Webster, K. E., O'Bryan, M. K., Fletcher, S., Crewther, P. E., Aapola, U., Craig, J., Harrison, D. K., Aung, H., Phutikanit, N., Lyle, R., Meachem, S. J., Antonarakis, S. E., de Kretser, D. M., Hedger, M. P., Peterson, P., Carroll, B. J., and Scott, H. S. (2005) Meiotic and epigenetic defects in Dnmt3L-knockout mouse spermatogenesis. Proc. Natl. Acad. Sci. U.S.A. 102, 4068-4073 (Pubitemid 40388556)
31. Kurts, C., Heath, W. R., Carbone, F. R., Allison, J., Miller, J. F., and Kosaka, H. (1996) Constitutive class I-restricted exogenous presentation of self antigens in vivo. J. Exp. Med. 184, 923-930 (Pubitemid 26313550)
32. Chang, Y. F., Imam, J. S., and Wilkinson, M. F. (2007) The nonsense-mediated decay RNA surveillance pathway. Annu. Rev. Biochem. 76, 51-74
33. Budde, S. M., van den Heuvel, L. P., Janssen, A. J., Smeets, R. J., Buskens, C. A., DeMeirleir, L., Van Coster, R., Baethmann, M., Voit, T., Trijbels, J. M., and Smeitink, J. A. (2000) Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene. Biochem. Biophys. Res. Commun. 275, 63-68 (Pubitemid 30663630)
34. Petruzzella, V., Vergari, R., Puzziferri, I., Boffoli, D., Lamantea, E., Zeviani, M., and Papa, S. (2001) A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome. Hum. Mol. Genet. 10, 529-535 (Pubitemid 32181676)
35. van den Heuvel, L., Ruitenbeek, W., Smeets, R., Gelman-Kohan, Z., Elpeleg, O., Loeffen, J., Trijbels, F., Mariman, E., de Bruijn, D., and Smeitink, J. (1998) Demonstration of a new pathogenic mutation in human complex I deficiency. A 5-bp duplication in the nuclear gene encoding the 18-kDa (AQDQ) subunit. Am. J. Hum. Genet. 62, 262-268 (Pubitemid 28110767)
36. Scacco, S., Petruzzella, V., Budde, S., Vergari, R., Tamborra, R., Panelli, D., van den Heuvel, L. P., Smeitink, J. A., and Papa, S. (2003) Pathological mutations of the human NDUFS4 gene of the 18-kDa (AQDQ) subunit of complex I affect the expression of the protein and the assembly and function of the complex. J. Biol. Chem. 278, 44161-44167 (Pubitemid 37377159)
37. Iuso, A., Scacco, S., Piccoli, C., Bellomo, F., Petruzzella, V., Trentadue, R., Minuto, M., Ripoli, M., Capitanio, N., Zeviani, M., and Papa, S. (2006) Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I. J. Biol. Chem. 281, 10374-10380 (Pubitemid 43864576)
38. Dunning, C. J., McKenzie, M., Sugiana, C., Lazarou, M., Silke, J., Connelly, A., Fletcher, J. M., Kirby, D. M., Thorburn, D. R., and Ryan, M. T. (2007) Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease. EMBO J. 26, 3227-3237 (Pubitemid 47057488)
39. Ogilvie, I., Kennaway, N. G., and Shoubridge, E. A. (2005) A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J. Clin. Invest. 115, 2784-2792 (Pubitemid 41434405)
40. Vogel, R. O., van den Brand, M. A., Rodenburg, R. J., van den Heuvel, L. P., Tsuneoka, M., Smeitink, J. A., and Nijtmans, L. G. (2007) Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI-deficient patients. Mol. Genet. Metab. 91, 176-182 (Pubitemid 46765172)
41. Lazarou, M., McKenzie, M., Ohtake, A., Thorburn, D. R., and Ryan, M. T. (2007) Analysis of the assembly profiles for mitochondrial and nuclear DNA-encoded subunits into complex I. Mol. Cell Biol. 27, 4228-4237 (Pubitemid 46906548)
42. Lawn, R. M., Wade, D. P., Garvin, M. R., Wang, X., Schwartz, K., Porter, J. G., Seilhamer, J. J., Vaughan, A. M., and Oram, J. F. (1999) The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J. Clin. Invest. 104, R25-31 (Pubitemid 29536327)
43. Berge, K. E., Tian, H., Graf, G. A., Yu, L., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., and Hobbs, H. H. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290, 1771-1775 (Pubitemid 32004809)
44. Gilbert, N., Bomar, J. M., Burmeister, M., and Moran, J. V. (2004) Characterization of a mutagenic B1 retrotransposon insertion in the jittery mouse. Hum. Mutat. 24, 9-13 (Pubitemid 38859219)
45. Druker, R., and Whitelaw, E. (2004) Retrotransposon-derived elements in the mammalian genome. A potential source of disease. J. Inherit. Metab. Dis. 27, 319-330 (Pubitemid 38756319)
46. Gu, Y., Kodama, H., Watanabe, S., Kikuchi, N., Ishitsuka, I., Ozawa, H., Fujisawa, C., and Shiga, K. (2007) The first reported case of Menkes disease caused by an Alu insertion mutation. Brain Dev. 29, 105-108 (Pubitemid 46162032)
47. Jurka, J. (1997) Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons. Proc. Natl. Acad. Sci. U.S.A. 94, 1872-1877
48. Cost, G. J., and Boeke, J. D. (1998) Targeting of human retrotransposon integration is directed by the specificity of the L1 endonuclease for regions of unusual DNA structure. Biochemistry 37, 18081-18093 (Pubitemid 29023965)
49. Dewannieux, M., Esnault, C., and Heidmann, T. (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat. Genet. 35, 41-48 (Pubitemid 37048594)
50. Dewannieux, M., and Heidmann, T. (2005) L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells. J. Mol. Biol. 349, 241-247 (Pubitemid 40693746)
51. Su, A. I., Cooke, M. P., Ching, K. A., Hakak, Y., Walker, J. R., Wiltshire, T., Orth, A. P., Vega, R. G., Sapinoso, L. M., Moqrich, A., Patapoutian, A., Hampton, G. M., Schultz, P. G., and Hogenesch, J. B. (2002) Large-scale analysis of the human and mouse transcriptomes. Proc. Natl. Acad. Sci. U.S.A. 99, 4465-4470 (Pubitemid 34286008)
52. Budde, S. M., van den Heuvel, L. P., Smeets, R. J., Skladal, D., Mayr, J. A., Boelen, C., Petruzzella, V., Papa, S., and Smeitink, J. A. (2003) Clinical heterogeneity in patients with mutations in the NDUFS4 gene of mitochondrial complex I. J. Inherit. Metab. Dis. 26, 813-815 (Pubitemid 38139383)
53. Calvaruso, M. A., Willems, P., van den Brand, M., Valsecchi, F., Kruse, S., Palmiter, R., Smeitink, J., and Nijtmans, L. (2012) Mitochondrial complex III stabilizes complex I in the absence of NDUFS4 to provide partial activity. Hum. Mol. Genet. 21, 115-120
54. DiMauro, S., and Schon, E. A. (2008) Mitochondrial disorders in the nervous system. Annu. Rev. Neurosci. 31, 91-123
55. Bélanger, M., Allaman, I., and Magistretti, P. J. (2011) Brain energy metabolism. Focus on astrocyte-neuron metabolic cooperation. Cell Metab. 14, 724-738
56. Davey, G. P., Peuchen, S., and Clark, J. B. (1998) Energy thresholds in brain mitochondria. Potential involvement in neurodegeneration. J. Biol. Chem. 273, 12753-12757 (Pubitemid 28246828)
57. Dubinsky, J. M. (2009) Heterogeneity of nervous system mitochondria. Location, location, location! Exp. Neurol. 218, 293-307
58. Ostergaard, E., Bradinova, I., Ravn, S. H., Hansen, F. J., Simeonov, E., Christensen, E., Wibrand, F., and Schwartz, M. (2005) Hypertrichosis in patients with SURF1 mutations. Am. J. Med. Genet. A 138, 384-388 (Pubitemid 41532959)
59. Kubota, Y., Ishii, T., Sugihara, H., Goto, Y., and Mizoguchi, M. (1999) Skin manifestations of a patient with mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS syndrome). J. Am. Acad. Dermatol. 41, 469-473 (Pubitemid 29418517)
60. Bodemer, C., Rötig, A., Rustin, P., Cormier, V., Niaudet, P., Saudubray, J. M., Rabier, D., Munnich, A., and de Prost, Y. (1999) Hair and skin disorders as signs of mitochondrial disease. Pediatrics 103, 428-433 (Pubitemid 29274537)
61. Silengo, M., Valenzise, M., Spada, M., Ferrero, G. B., Ferraris, S., Dassi, P., and Jarre, L. (2003) Hair anomalies as a sign of mitochondrial disease. Eur. J. Pediatr. 162, 459-461 (Pubitemid 36904266)
62. Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., Törnell, J., Jacobs, H. T., and Larsson, N. G. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417-423 (Pubitemid 38715133)
63. Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., Morrow, J. D., Van Remmen, H., Sedivy, J. M., Yamasoba, T., Tanokura, M., Weindruch, R., Leeuwenburgh, C., and Prolla, T. A. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309, 481-484 (Pubitemid 40994689)
64. Mckenzie, M., and Ryan, M. T. (2010) Assembly factors of human mitochondrial complex I and their defects in disease. IUBMB Life 62, 497-502
65. Matern, D. (2008) 3.2 Acylcarnitines, Including in Vitro Loading Tests. in Laboratory Guide to the Methods in Biochemical Genetics, 26th Ed. (Blau, N., Duran, M., and Gibson, K. M. eds.) pp. 171-206, Springer Verlag, Berlin
66. Houten, S. M., and Wanders, R. J. (2010) A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. J. Inherit. Metab. Dis. 33, 469-477
67. Rubio-Gozalbo, M. E., Sengers, R. C., Trijbels, J. M., Doesburg, W. H., Janssen, A. J., Verbeek, A. L., and Smeitink, J. A. (2000) A prognostic index as diagnostic strategy in children suspected of mitochondriocytopathy. Neuropediatrics 31, 114-121 (Pubitemid 30495434)
68. Naini, A., Kaufmann, P., Shanske, S., Engelstad, K., De Vivo, D. C., and Schon, E. A. (2005) Hypocitrullinemia in patients with MELAS. An insight into the "MELAS paradox." J. Neurol. Sci. 229, 187-193 (Pubitemid 40347254)
69. Parfait, B., de Lonlay, P., von Kleist-Retzow, J. C., Cormier-Daire, V., Chrétien, D., Rötig, A., Rabier, D., Saudubray, J. M., Rustin, P., and Munnich, A. (1999) The neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome mtDNA mutation (T8993G) triggers muscle ATPase deficiency and hypocitrullinemia. Eur. J. Pediatr. 158, 55-58 (Pubitemid 29143580)
70. Morava, E., Hogeveen, M., De Vries, M., Ruitenbeek, W., de Boode, W. P., and Smeitink, J. (2006) Normal serum alanine concentration differentiates transient neonatal lactic acidemia from an inborn error of energy metabolism. Biol. Neonate 90, 207-209 (Pubitemid 44427042)