{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:01:33Z","timestamp":1781938893011,"version":"3.54.5"},"reference-count":92,"publisher":"Portland Press Ltd.","issue":"1-3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,6,13]]},"abstract":"<jats:p>Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that determine an impairment of the electron transport chain functioning. Diagnosis often requires a complex approach with measurements of serum lactate, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement. Exercise intolerance is a common symptom of MD, due to increased dependence of skeletal muscle on anaerobic metabolism, with an excess lactate generation, phosphocreatine depletion, enhanced free radical production, reduced oxygen extraction and electron flux through the respiratory chain. MD treatment has included antioxidants (vitamin E, alpha lipoic acid), coenzyme Q10, riboflavin, creatine monohydrate, dichloroacetate and exercise training. Exercise is a particularly important tool in diagnosis as well as in the management of these diseases.<\/jats:p>","DOI":"10.1007\/s10540-007-9037-0","type":"journal-article","created":{"date-parts":[[2007,5,10]],"date-time":"2007-05-10T14:26:30Z","timestamp":1178807190000},"page":"53-67","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Functional Diagnostics in Mitochondrial Diseases"],"prefix":"10.1042","volume":"27","author":[{"given":"Gabriele","family":"Siciliano","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Volpi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Murri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Neurology, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2007,6,13]]},"reference":[{"key":"9037_CR1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1093\/hmg\/ddg038","volume":"12","author":"A Agostino","year":"2003","unstructured":"Agostino A, Invernizzi F, Tiveron C, Fagiolari G, Prelle A, Lamantea E, Giavazzi A, Battaglia G, Tatangelo L, Tiranti V, Zeviani M (2003) Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice. Hum Mol Genet 12:399\u2013413","journal-title":"Hum Mol Genet"},{"key":"9037_CR2","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1212\/01.WNL.0000056088.09408.3C","volume":"60","author":"A Agostino","year":"2003","unstructured":"Agostino A, Valletta L, Chinnery PF, Ferrari G, Carrara F, Taylor RW, Schaefer AM, Turnbull DM, Tiranti V, Zeviani M (2003) Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology 60:1354\u20131356","journal-title":"Neurology"},{"key":"9037_CR3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/j.1748-1716.1977.tb10361.x","volume":"99","author":"P Andersen","year":"1977","unstructured":"Andersen P, Henriksson J (1977) Training induced changes in the subgroups of human type II skeletal muscle fibres. Acta Physiol Scand 99:123\u2013125","journal-title":"Acta Physiol Scand"},{"key":"9037_CR4","doi-asserted-by":"crossref","unstructured":"Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR,Drouin J, Eperon IC,Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (1981) Sequence and organization. Nature 290(5806):457\u2013465","DOI":"10.1038\/290457a0"},{"key":"9037_CR5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1086\/345489","volume":"72","author":"H Antonicka","year":"2003","unstructured":"Antonicka H, Leary SC, Guercin GH, Agar JN, Horvath R, Kennaway NG, Harding CO, Jaksch M, Shoubridge EA (2003) Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am J Hum Genet 72:101\u2013114","journal-title":"Am J Hum Genet"},{"key":"9037_CR6","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1093\/hmg\/ddl106","volume":"15","author":"H Antonicka","year":"2006","unstructured":"Antonicka H, Sasarman F, Kennway NG, Shoubridge EA (2006) The molecular basis for tissue specificity of the oxidative phosphorylation deficiencies in patients with mutations in the mitochondrial translation factor EFG1. Hum Mol Genet 15:1835\u20131846","journal-title":"Hum Mol Genet"},{"key":"9037_CR7","first-page":"257","volume":"37","author":"Z Argov","year":"1987","unstructured":"Argov Z, Bank WJ, Maris J, Peterson P, Chance B (1987) Bioenergetic heterogeneity of human mitochondrial myopathies: phosphorus magnetic resonance spectroscopy study. Neurobiology 37:257\u2013262","journal-title":"Neurobiology"},{"key":"9037_CR8","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1002\/1097-4598(200009)23:9<1316::AID-MUS2>3.0.CO;2-I","volume":"23","author":"Z Argov","year":"2000","unstructured":"Argov Z, Lofberg M, Arnold DL (2000) Insights into muscle diseases gained by phosphorus magnetic resonance spectroscopy. Muscle Nerve 23:1316\u20131334","journal-title":"Muscle Nerve"},{"key":"9037_CR9","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1212\/01.WNL.0000134607.76780.B2","volume":"63","author":"K Aure","year":"2004","unstructured":"Aure K, Benoist JF, de Ogier Baulny H, Romero NB, Rigal O, Lombes A (2004) Progression despite replacement of a myopathic form of coenzyme Q10 defect. Neurology 63:727\u2013729","journal-title":"Neurology"},{"key":"9037_CR47","doi-asserted-by":"crossref","unstructured":"Bai R-K, Wong L-JC (2000) Simultaneous detection and quantification of mitochondrial dna deletion(s), depletion, and over- replication in patients with mitochondrial disease. J Mol Diagn 7:613\u2013622","DOI":"10.1016\/S1525-1578(10)60595-8"},{"key":"9037_CR10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/emboj\/21.1.43","volume":"21","author":"A Barrientos","year":"2002","unstructured":"Barrientos A, Korr D, Tzagoloff A (2002) Shy1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh\u2019s syndrome. EMBO J 21:43\u201352","journal-title":"EMBO J"},{"key":"9037_CR11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/ng1073","volume":"33","author":"BJ Battersby","year":"2003","unstructured":"Battersby BJ, Coredo-Osti JC, Shoubridge EA (2003) Nuclear genetic control of mitochondrial DNA segregation. Nat Genet 33:183\u2013186","journal-title":"Nat Genet"},{"key":"9037_CR12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/mus.880070902","volume":"7","author":"B Bigland-Ritchie","year":"1984","unstructured":"Bigland-Ritchie B, Woods JJ (1984) Changes in muscle contractile properties and neural control during human muscular fatigue. Muscle Nerve 7:691\u2013699","journal-title":"Muscle Nerve"},{"key":"9037_CR82","doi-asserted-by":"crossref","unstructured":"Bohr VA, Stevnsner T, de Souza-Pinto NC (2002) Mitochondrial DNA repair of oxidative damage in mammalian cells. Gene 286:127\u2013134","DOI":"10.1016\/S0378-1119(01)00813-7"},{"key":"9037_CR13","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/j.1432-1033.1993.tb18342.x","volume":"217","author":"G Bonne","year":"1993","unstructured":"Bonne G, Seibel P, Possekel S, Marsac C, Kadenbach B (1993) Expression of human cytochrome c oxidase subunits during fetal development. Eur J Biochem 217:1099\u20131107","journal-title":"Eur J Biochem"},{"key":"9037_CR14","first-page":"1187","volume":"51","author":"L Boulet","year":"1992","unstructured":"Boulet L, Karpati G, Shoubridge EA (1992) Distribution and threshold expression of the tRNA(Lys) mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF). Am J Hum Genet 51:1187\u20131200","journal-title":"Am J Hum Genet"},{"key":"9037_CR15","doi-asserted-by":"crossref","first-page":"4502","DOI":"10.1093\/nar\/29.21.4502","volume":"29","author":"Z Cao","year":"2001","unstructured":"Cao Z, Wanagat J, McKiernan SH, Aiken JM (2001) Mitochondrial DNA deletion mutations are concomitant with ragged red regions of individual, aged muscle fibers: analysis by laser-capture microdissection. Nucleic Acids Res 29:4502\u20134508","journal-title":"Nucleic Acids Res"},{"key":"9037_CR16","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/mus.20368","volume":"32","author":"P Cejudo","year":"2005","unstructured":"Cejudo P, Bautista J, Montemayor T, Villagomez R, Jimenez L, Ortega F, Campos Y, Sanchez H, Arenas J (2005) Exercise training in mitochondrial myopathy: a randomized controlled trial. Muscle Nerve 32:342\u2013350","journal-title":"Muscle Nerve"},{"key":"9037_CR17","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev.cb.07.110191.002321","volume":"7","author":"DA Clayton","year":"1992","unstructured":"Clayton DA (1992) Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol 7:453\u2013478","journal-title":"Annu Rev Cell Biol"},{"key":"9037_CR18","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1212\/WNL.57.3.515","volume":"57","author":"S Di Giovanni","year":"2001","unstructured":"Di Giovanni S, Mirabella M, Spinazzola A, Crociani P, Silvestri G, Broccolini A, Tonali P, Di Mauro S, Servidei S (2001) Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57:515\u2013518","journal-title":"Neurology"},{"key":"9037_CR19","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/ana.410170602","volume":"17","author":"S Di Mauro","year":"1985","unstructured":"Di Mauro S, Bonilla E, Zeviani M, Nakagawa M, De Vivo DC (1985) Mitochondrial myopathies. Ann Neurol 17:521\u2013538","journal-title":"Ann Neurol"},{"key":"9037_CR20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/BF01799110","volume":"19","author":"S DiMauro","year":"1996","unstructured":"DiMauro S (1996) Mitochondrial myopathies: what next? J Inher Metab Dis 19:489\u2013503","journal-title":"J Inher Metab Dis"},{"key":"9037_CR21","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1001\/archneur.1993.00540110075008","volume":"50","author":"S Di Mauro","year":"1993","unstructured":"Di Mauro S, Moraes CT (1993) Mitochondrial encephalomyopathies. Arch Neurol 50:1197\u20131208","journal-title":"Arch Neurol"},{"key":"9037_CR22","first-page":"1","volume-title":"Human muscle fatigue: physiological mechanisms. Ciba Foundation Symposium 82","author":"RHT Edwards","year":"1981","unstructured":"Edwards RHT (1981) Human muscle function and fatigue. In: Porter R, Whelan J (eds) Human muscle fatigue: physiological mechanisms. Ciba Foundation Symposium 82. Pitman Medical, London, pp 1\u201318"},{"key":"9037_CR23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1055\/s-2008-1040954","volume":"16","author":"R Fadic","year":"1996","unstructured":"Fadic R, Johns DR (1996) Clinical spectrum of mitochondrial diseases. Sem Neurol 16:11\u201322","journal-title":"Sem Neurol"},{"key":"9037_CR24","first-page":"163","volume":"15","author":"J Finsterer","year":"2000","unstructured":"Finsterer J, Obermann I, Milvay E (2000) Diagnostis yeald of the lactate stress test in 160 patients with suspected respiratory chain disorder. Metab Brain Dis 15:163\u2013171","journal-title":"Metab Brain Dis"},{"key":"9037_CR25","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00415-003-0993-4","volume":"250","author":"T Dysgaard Jeppesen","year":"2003","unstructured":"Dysgaard Jeppesen T, Olsen D, Vissing J (2003) Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy. J Neurol 250:293\u2013299","journal-title":"J Neurol"},{"key":"9037_CR26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0031-3955(03)00115-9","volume":"49","author":"L Gillis","year":"2002","unstructured":"Gillis L, Kaye E (2002). Diagnosis and management of mitochondrial diseases. Pediatr Clin N Am 49:203\u2013219","journal-title":"Pediatr Clin N Am"},{"key":"9037_CR27","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1210\/jc.2002-020525","volume":"87","author":"AP Gimenez-Roqueplo","year":"2002","unstructured":"Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rotig A, Jeunemaitre X (2002) Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J Clin Endocrinol Metab 87:4771\u20134774","journal-title":"J Clin Endocrinol Metab"},{"key":"9037_CR28","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1212\/01.WNL.0000113719.67643.B7","volume":"62","author":"M Gironi","year":"2004","unstructured":"Gironi M, Lamperti C, Nemni R, Moggio M, Comi G, Guerini FR, Ferrante P, Canal N, Naini A, Bresolin N, DiMauro S (2004) Late-onset cerebellar ataxia with hypogonadism and muscle coenzyme Q10 deficiency. Neurology 62:818\u2013820","journal-title":"Neurology"},{"key":"9037_CR29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2165\/00007256-200333110-00001","volume":"33","author":"I Irrcher","year":"2003","unstructured":"Irrcher I, Adhihetty PJ, Joseph AM, Ljubicic V, Hood DA (2003) Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med 33:783\u2013793","journal-title":"Sports Med"},{"key":"9037_CR30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0022-510X(93)90326-T","volume":"116","author":"GJ Kemp","year":"1993","unstructured":"Kemp GJ, Taylor DJ, Dunn JF, Frostick SP, Radda GK (1993a) Cellular energetics of dystrophic muscle. J Neurol Sci 116:201\u2013206","journal-title":"J Neurol Sci"},{"key":"9037_CR31","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/nbm.1940060504","volume":"6","author":"GJ Kemp","year":"1993","unstructured":"Kemp GJ, Taylor DJ, Thompson CH et al (1993b) Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal mitochondrial oxidation in skeletal muscle during recovery from exercise. NMR Biomed 6:302\u2013310","journal-title":"NMR Biomed"},{"key":"9037_CR32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1748-1716.1981.tb06854.x","volume":"113","author":"K Klausen","year":"1981","unstructured":"Klausen K, Andersen LB, Pelle I (1981) Adaptive changes in work capacity, skeletal muscle capillarization and enzyme levels during training and detraining. Acta Physiol Scand 113:9\u201316","journal-title":"Acta Physiol Scand"},{"key":"9037_CR33","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/j.1468-1331.2004.00970.x","volume":"12","author":"C Kornblum","year":"2005","unstructured":"Kornblum C, Schroder R, Muller K, Vorgerd M, Eggers J, Bogdanow M, Papassotiropoulos A, Fabian K, Klockgether T, Zange J (2005) Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study. Eur J Neurol 12:300\u2013309","journal-title":"Eur J Neurol"},{"key":"9037_CR34","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/archneur.62.2.317","volume":"62","author":"SR Lalani","year":"2005","unstructured":"Lalani SR, Vladutiu GD, Plunkett K, Lotze TE, Adesina AM, Scaglia F (2005) Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch Neurol 62:317\u2013320","journal-title":"Arch Neurol"},{"key":"9037_CR35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ana.10278","volume":"52","author":"E Lamantea","year":"2002","unstructured":"Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M (2002) Mutations of mitochondrial DNA polymerase A are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol 52:211\u2013219","journal-title":"Ann Neurol"},{"key":"9037_CR36","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1212\/01.WNL.0000055089.39373.FC","volume":"60","author":"C Lamperti","year":"2003","unstructured":"Lamperti C, Naini A, Hirano M, De Vivo DC, Bertini E, Servidei S, Valeriani M, Lynch D, Banwell B, Berg M, Dubrovsky T, Chiriboga C, Angelini C, Pegoraro E, DiMauro S (2003) Cerebellar ataxia and coenzyme Q10 deficiency. Neurology 60:1206\u20131208","journal-title":"Neurology"},{"key":"9037_CR37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0140-6736(99)05225-3","volume":"355","author":"JV Leonard","year":"2000","unstructured":"Leonard JV, Schapira AHV (2000a) Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet 355:299\u2013304","journal-title":"Lancet"},{"key":"9037_CR38","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S1474-4422(02)00159-X","volume":"1","author":"R McFarland","year":"2002","unstructured":"McFarland R, Taylor RW, Turnbull DM (2002) The neurology of mitochondrial DNA disease. Lancet Neurol 1:343\u2013351","journal-title":"Lancet Neurol"},{"key":"9037_CR39","doi-asserted-by":"crossref","first-page":"E580","DOI":"10.1152\/ajpendo.2000.278.4.E580","volume":"278","author":"S McKenzie","year":"2000","unstructured":"McKenzie S, Philips SM, Carter SL, Lowther S, Gibala MJ, Tarnopolsky MA (2000) Endurance exercise training attenuates leucine oxidation and BCOAD activation durino exercise in humans. Am J Physiol Endocrinol Metab 278:E580\u2013E587","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"9037_CR40","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/BF00238555","volume":"71","author":"HSH Mac Rae","year":"1995","unstructured":"Mac Rae HSH, Noakes TD, Dennis SC (1995) Role of decreased carbohydrate oxidation on slower rises in ventilation with increasing exercise intensity after training. Eur J Appl Physiol 71:523\u2013529","journal-title":"Eur J Appl Physiol"},{"key":"9037_CR41","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1212\/01.WNL.0000028689.93049.9A","volume":"59","author":"M Mancuso","year":"2002","unstructured":"Mancuso M, Salviati L, Sacconi S, Otaegui D, Camano P, Marina A, Bacman S, Moraes CT, Carlo JR, Garcia M, Garcia-Alvarez M, Monzon L, Naini AB, Hirano M, Bonilla E, Taratuto AL, DiMauro S, Vu TH (2002) Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA. Neurology 59:1197\u20131202","journal-title":"Neurology"},{"key":"9037_CR42","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1212\/WNL.56.7.849","volume":"56","author":"O Musumeci","year":"2001","unstructured":"Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, Weissman BM, Tsao CY, Mendell JR, Shanske S, De Vivo DC, Hirano M, DiMauro S (2001) Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology 56:849\u2013855","journal-title":"Neurology"},{"key":"9037_CR43","doi-asserted-by":"crossref","unstructured":"Naccarati A, Molinu S, Mancuso M, Siciliano G, Migliore L (2000) Cytogenetic damage in peripheral lymphocytes of mitochondrial disease patients. Neurol Sci 21:S963\u2013S965","DOI":"10.1007\/s100720070010"},{"key":"9037_CR44","doi-asserted-by":"crossref","unstructured":"Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, Januszewicz A, Eng C, Smith WM, Munk R, Manz T, Glaesker S, Apel TW, Treier M, Reineke M, Walz MK, Hoang-Vu C, Brauckhoff M, Klein-Franke A, Klose P, Schmidt H, Maier-Woelfle M, Peczkowska M, Szmigielski C, Eng C, Freiburg-Warsaw-Columbus Pheochromocytoma Study Group (2002) Germ-line mutations in nonsyndromic phaeochromocytoma. N Engl J Med 346:1459\u20131466","DOI":"10.1056\/NEJMoa020152"},{"key":"9037_CR45","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1212\/01.WNL.0000150584.45055.27","volume":"64","author":"DB Olsen","year":"2005","unstructured":"Olsen DB, Orngreen MC, Vissing J (2005) Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy. Neurology 64:1064\u20131066","journal-title":"Neurology"},{"key":"9037_CR46","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1002\/ana.20460","volume":"57","author":"MC Orngreen","year":"2005","unstructured":"Orngreen MC, Olsen DB, Vissing J (2005) Aerobic training in patients with myotonic dystrophy type 1. Ann Neurol 57:754\u2013757","journal-title":"Ann Neurol"},{"issue":"3","key":"9037_CR48","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1309\/WATB-W4QV-NA53-B9MY","volume":"116","author":"S Rollins","year":"2001","unstructured":"Rollins S, Prayson RA,McMahon JT, Cohen BH (2001) Diagnostic yield muscle biopsy in patients with clinical evidence of mitochondrial cytopathy. Am J Clin Pathol 116(3):326\u2013330","journal-title":"Am J Clin Pathol"},{"key":"9037_CR49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0140-6736(00)02531-9","volume":"356","author":"A Rotig","year":"2000","unstructured":"Rotig A, Appelkvist EL, Geromel V, Chretien D, Kadhom N, Edery P, Lebideau M, Dallner G, Munnich A, Ernster L, Rustin P (2000) Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency. Lancet 356:391\u2013395","journal-title":"Lancet"},{"key":"9037_CR50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0005-2728(01)00228-6","volume":"1553","author":"P Rustin","year":"2002","unstructured":"Rustin P, Rotig A (2002) Inborn errors of complex II: unusual human mitochondrial diseases. Biochim Biophys Acta 1553:117\u2013122","journal-title":"Biochim Biophys Acta"},{"key":"9037_CR51","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1001\/archneur.59.5.862","volume":"59","author":"L Salviati","year":"2002","unstructured":"Salviati L, Sacconi S, Rasalan MM, Kronn DF, Braun A, Canoll P, Davidson M, Shanske S, Bonilla E, Hays AP, Schon EA, DiMauro S (2002a) Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease. Arch Neurol 59:862\u2013865","journal-title":"Arch Neurol"},{"key":"9037_CR52","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/bj3630321","volume":"363","author":"L Salviati","year":"2002","unstructured":"Salviati L, Hernandez-Rosa E, Walker WF, Sacconi S, DiMauro S, Schon EA, Davidson MM (2002b) Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations. Biochem J 363:321\u2013327","journal-title":"Biochem J"},{"key":"9037_CR53","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ana.10284","volume":"52","author":"L Salviati","year":"2002","unstructured":"Salviati L, Sacconi S, Mancuso M, Otaegui D, Camano P, Marina A, Rabinowitz S, Shiffman R, Thompson K, Wilson CM, Feigenbaum A, Naini AB, Hirano M, Bonilla E, DiMauro S, Vu TH (2002c) Mitochondrial DNA depletion and dGK gene mutations. Ann Neurol 52:311\u2013317","journal-title":"Ann Neurol"},{"key":"9037_CR54","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1212\/01.wnl.0000172859.55579.a7","volume":"65","author":"L Salviati","year":"2005","unstructured":"Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, Basso G, Quinzii C, Angelini C, Hirano M, Naini AB, Navas P, DiMauro S, Montini G (2005) Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition. Neurology 65:606\u2013608","journal-title":"Neurology"},{"key":"9037_CR55","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1432-1033.1995.0235i.x","volume":"230","author":"H Schagger","year":"1995","unstructured":"Schagger H, Noack H, Halangk W, Brandt U, von Jagow G (1995) Cytochrome-c oxidase in developing rat heart. Enzymic properties and amino-terminal sequences suggest identity of the fetal heart and the adult liver isoform. Eur J Biochem 230:235\u2013241","journal-title":"Eur J Biochem"},{"key":"9037_CR56","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/ana.10176","volume":"51","author":"M Schlame","year":"2002","unstructured":"Schlame M, Towbin JA, Heerdt PM, Jehle R, DiMauro S, Blanck TJ (2002) Deficiency of tetralinoleoylcardiolipin in Barth syndrome. Ann Neurol 51:634\u2013637","journal-title":"Ann Neurol"},{"key":"9037_CR57","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/(SICI)1097-4598(199811)21:11<1374::AID-MUS3>3.0.CO;2-6","volume":"21","author":"M Sciacco","year":"1998","unstructured":"Sciacco M, Gasparo-Rippa P, Vu TH, Tanji K, Shanske S, Mendell JR, Schon EA, DiMauro S, Bonilla E (1998) Study of mitochondrial DNA depletion in muscle by single-fiber polymerase chain reaction. Muscle Nerve 21:1374\u20131381","journal-title":"Muscle Nerve"},{"key":"9037_CR58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0014-5793(01)02574-1","volume":"500","author":"H Shitara","year":"2001","unstructured":"Shitara H, Kaneda H, Sato A, Iwasaki K, Hayashi J-I, Taya C, Yonekawa H (2001) Non-invasive visualization of sperm mitochondria behaviour in transgenic mice with introduced green fluorescent protein (GFP). FEBS Lett 500:7\u201311","journal-title":"FEBS Lett"},{"key":"9037_CR59","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-1-4757-9065-8_5","volume":"19","author":"JM Shoffner","year":"1990","unstructured":"Shoffner JM, Wallace DC (1990) Oxidative phosphorylation diseases disorders of two genomes. Adv Hum Genet 19:267\u2013330","journal-title":"Adv Hum Genet"},{"key":"9037_CR60","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1093\/hmg\/6.13.2239","volume":"6","author":"EA Shoubridge","year":"1997","unstructured":"Shoubridge EA, Johns T, Karpati G (1997) Complete restoration of a wild-type mtDNA genotype in regenerating muscle fibres in a patient with a tRNA point mutation and mitochondrial encephalomyopathy. Hum Mol Genet 6:2239\u20132242","journal-title":"Hum Mol Genet"},{"key":"9037_CR61","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0092-8674(90)90238-A","volume":"62","author":"EA Shoubridge","year":"1990","unstructured":"Shoubridge EA, Karpati G, Hastings KE (1990) Deletion mutants are functionally dominant over wild-type mitochondrial genomes in skeletal muscle fiber segments in mitochondrial disease. Cell 62:43\u201349","journal-title":"Cell"},{"key":"9037_CR62","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0960-8966(99)00047-4","volume":"9","author":"G Siciliano","year":"1999","unstructured":"Siciliano G, Renna M, Manca ML, Prontera C, Zucchelli G, Ferrannini E, Murri L (1999) The relationship of plasma catecholamine and lactate during anaerobic threshold exercise in mitochondrial myopathies. Neuromuscul Disord 9:411\u2013416","journal-title":"Neuromuscul Disord"},{"key":"9037_CR63","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0960-8966(99)00068-1","volume":"10","author":"G Siciliano","year":"2000","unstructured":"Siciliano G, Manca ML, Renna M, Prontera C, Mercuri A, Murri L (2000) Effects of aerobic training on lactate and catecholaminergic exercise responses in mitochondrial myopathies. Neuromuscul Disord 10:40\u201345","journal-title":"Neuromuscul Disord"},{"key":"9037_CR64","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1748-1716.1976.tb10247.x","volume":"97","author":"B Sjodin","year":"1976","unstructured":"Sjodin B, Thorstensson A, Frith K, Karlsson J (1976) Effect of physical training on LDH activity and LDH isozyme pattern in human skeletal muscle. Acta Physiol Scand 97:150\u2013157","journal-title":"Acta Physiol Scand"},{"key":"9037_CR65","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1212\/WNL.48.5.1238","volume":"48","author":"C Sobreira","year":"1997","unstructured":"Sobreira C, Hirano M, Shanske S, Keller RK, Haller RG, Davidson E, Santorelli FM, Miranda AF, Bonilla E, Mojon DS, Barreira AA, King MP, DiMauro S (1997) Mitochondrial encephalomyopathy with coenzyme Q10 deficiency. Neurology 48:1238\u20131243","journal-title":"Neurology"},{"key":"9037_CR66","first-page":"93","volume":"109","author":"W Sperl","year":"1997","unstructured":"Sperl W (1997) Diagnosis and therapy of mitochondriopathies. Wien Klin Wochenschr 109:93\u201399","journal-title":"Wien Klin Wochenschr"},{"key":"9037_CR67","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1095\/biolreprod63.2.582","volume":"63","author":"P Sutovsky","year":"2000","unstructured":"Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G (2000) Ubiquitinated sperm mitochondria, selective proteolysis and the regulation of mitochondrial inheritance in mammalian embryos. Biol of Reproduct 63:582\u2013590","journal-title":"Biol of Reproduct"},{"key":"9037_CR68","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0925-4439(92)90095-5","volume":"1139","author":"JW Taanman","year":"1992","unstructured":"Taanman JW, Herzberg NH, De Vries H, Bolhuis PA, Van den Bogert C (1992) Steady-state transcript levels of cytochrome c oxidase genes during human myogenesis indicate subunit switching of subunit Via and co-expression of subunit VIIa isoforms. Biochim Biophys Acta 1139:155\u2013162","journal-title":"Biochim Biophys Acta"},{"key":"9037_CR69","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1212\/WNL.47.2.529","volume":"47","author":"T Taivassalo","year":"1996","unstructured":"Taivassalo T, Matthews PM, De Stefano N, Sripathi N, Genge A, Karpati G, Arnold DL (1996) Combined aerobic training and dichloroacetate improve exercise capacity and indices of aerobic metabolism in muscle cytochrome oxidase deficiency. Neurology 47:529\u2013534","journal-title":"Neurology"},{"key":"9037_CR70","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1212\/WNL.50.4.1055","volume":"50","author":"T Taivassalo","year":"1998","unstructured":"Taivassalo T, De Stefano N, Argov Z, Matthews PM, Chen J, Genge A, Karpati G, Arnold DL (1998) Effects of aerobic training in patients with mitochondrial myopathies. Neurology 50:1055\u20131060","journal-title":"Neurology"},{"key":"9037_CR71","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/ana.1050","volume":"50","author":"T Taivassalo","year":"2001","unstructured":"Taivassalo T, Shoubridge EA, Chen J, Kennaway NG, DiMauro S, Arnold DL, Haller RG (2001) Aerobic conditioning in patients with mitochondrial myopathies: physiological, biochemical, and genetic effects. Ann Neurol 50:133\u2013141","journal-title":"Ann Neurol"},{"key":"9037_CR72","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/brain\/awg028","volume":"126","author":"T Taivassalo","year":"2003","unstructured":"Taivassalo T, Jensen TD, Kennaway N, DiMauro S, Vissing J, Haller RG (2003) The spectrum of exercise tolerance in mitochondrial myopathies: a study of 40 patients. Brain 126: 413","journal-title":"Brain"},{"issue":"Pt 12","key":"9037_CR73","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1093\/brain\/awl282","volume":"129","author":"T Taivassalo","year":"2006","unstructured":"Taivassalo T, Gardner JL, Taylor RW, Schaefer AM, Newman J, Barron MJ, Haller RJ, Turnbull DM (2006) Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions. Brain 129(Pt 12):3391\u20133401","journal-title":"Brain"},{"key":"9037_CR92","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1128\/MCB.22.21.7614-7621.2002","volume":"22","author":"Y Takahashi","year":"2002","unstructured":"Takahashi Y, Kako K, Kashiwabara S, Takehara A, Inada Y, Arai H, Nakada K, Kodama H, Hayashi J, Baba T, Munekata E (2002) Mammalian copper chaperone Cox17p has an essential role in activation of cytochrome C oxidase and embryonic development. Mol Cell Biol 22:7614\u20137621","journal-title":"Mol Cell Biol"},{"key":"9037_CR75","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.mito.2004.07.011","volume":"4","author":"M Tarnopolsky","year":"2004","unstructured":"Tarnopolsky M (2004) Exercise testing as a diagnostic entit\u00e0 in mitochondrial myopathies. Mitochondrion 4:529\u2013542","journal-title":"Mitochondrion"},{"key":"9037_CR74","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.1028","volume":"49","author":"MA Tarnopolsky","year":"2001","unstructured":"Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49:561\u2013574","journal-title":"Ann Neurol"},{"key":"9037_CR91","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1249\/01.mss.0000177341.89478.06","volume":"37","author":"MA Tarnopolsky","year":"2005","unstructured":"Tarnopolsky MA, RaHa S (2005) Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. Med Sci Sports Exerc 37:2086\u20132093","journal-title":"Med Sci Sports Exerc"},{"key":"9037_CR76","unstructured":"The Mitochondrial Disease Foundation (2003) Pittsburgh.info@umdf.org"},{"key":"9037_CR77","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0891-5849(99)00132-X","volume":"27","author":"M Tomasetti","year":"1999","unstructured":"Tomasetti M, Littarru GP, Stocker R, Alleva R (1999) Coenzyme Q10 enrichment decreases oxidative DNA damage in human lymphocytes. Free Radic Biol Med 27:1027\u20131032","journal-title":"Free Radic Biol Med"},{"key":"9037_CR78","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/ajmg.1397","volume":"106","author":"RH Triepels","year":"2001","unstructured":"Triepels RH, van Den Heuvel LP, Trijbels JM, Smeitink JA (2001) Respiratory chain complex I deficiency. Am J Med Genet 106:37\u201345","journal-title":"Am J Med Genet"},{"key":"9037_CR79","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1146\/annurev.bi.55.070186.001341","volume":"55","author":"A Tzagoloff","year":"1986","unstructured":"Tzagoloff A, Myers AM (1986) Genetics of mitochondria biogenesis. Annu Rev Biochem 55:249\u2013285","journal-title":"Annu Rev Biochem"},{"key":"9037_CR80","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0960-8966(02)00216-X","volume":"13","author":"G Goethem Van","year":"2003","unstructured":"Van Goethem G, Martin JJ, Dermaut B, Lofgren A, Wibail A, Ververken D, Tack P, Dehaene I, Van Zandijcke M, Moonen M, Ceuterick C, De Jonghe P, Van Broeckhoven C (2003) Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord 13:133\u2013142","journal-title":"Neuromuscul Disord"},{"key":"9037_CR81","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/ana.10371","volume":"l52","author":"L Maldergem Van","year":"2002","unstructured":"Van Maldergem L, Trijbels F, DiMauro S, Sindelar PJ, Musumeci O, Janssen A, Delberghe X, Martin JJ, Gillerot Y (2002) Coenzyme Q-responsive Leigh\u2019s encephalopathy in two sisters. Ann Neuro l52:750\u2013754","journal-title":"Ann Neuro"},{"key":"9037_CR83","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1086\/342773","volume":"71","author":"I Visapaa","year":"2002","unstructured":"Visapaa I, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L (2002) GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. Am J Hum Genet 71:863\u2013876","journal-title":"Am J Hum Genet"},{"key":"9037_CR84","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/ana.10725","volume":"54","author":"J Vissing","year":"2003","unstructured":"Vissing J, Haller RG (2003) A diagnostic cycle test for McArdle\u2019s disease. Ann Neurol 54:539\u2013542","journal-title":"Ann Neurol"},{"key":"9037_CR85","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000117269","volume":"36","author":"UA Walker","year":"1996","unstructured":"Walker UA, Collins S, Byrne E (1996) Respiratory chain encephalomyopathies: a diagnostic classification. Eur Neurol 36:260\u2013267","journal-title":"Eur Neurol"},{"key":"9037_CR86","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1126\/science.283.5407.1482","volume":"283","author":"DC Wallace","year":"1999","unstructured":"Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482\u20131488","journal-title":"Science"},{"key":"9037_CR87","doi-asserted-by":"crossref","unstructured":"Wang Y, Michikawa Y, Mallidis C, Bai Y, Woodhouse L,Y arasheski KE, Miller CA, Askanas V, Engel WK, Bhasin S, Attardi G (2001) Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication. Proc Natl Acad Sci USA 27; 98(7):4022\u20134077","DOI":"10.1073\/pnas.061013598"},{"key":"9037_CR88","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1152\/jappl.1973.35.2.236","volume":"35","author":"K Wasserman","year":"1973","unstructured":"Wasserman K, Whipp BJ, Koyal SN, Beaver WL (1973) Anaerobic threshold and respiratory gas exchange during exercise. J Appl Physiol 35:236\u2013243","journal-title":"J Appl Physiol"},{"key":"9037_CR89","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1097\/00005768-199705000-00013","volume":"29","author":"A Weltman","year":"1997","unstructured":"Weltman A, Weltman JY, Womack CJ, Davis SE, Blumer JL, Gaesser GA, Hartman ML (1997) Exercise training decreases the growth hormone (GH) response to acute constant-load exercise. Med Sci Sports Exerc 29:669\u2013676","journal-title":"Med Sci Sports Exerc"},{"key":"9037_CR90","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1097\/00019052-200310000-00004","volume":"16","author":"M Zeviani","year":"2003","unstructured":"Zeviani M, Carelli V (2003) Mitochondrial disorders. Curr Opin Neurol 16:585\u2013594","journal-title":"Curr Opin Neurol"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/27\/1-3\/53\/474452\/bsr0270053.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/27\/1-3\/53\/474452\/bsr0270053.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T18:11:34Z","timestamp":1637086294000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/27\/1-3\/53\/55769\/Functional-Diagnostics-in-Mitochondrial-Diseases"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,13]]},"references-count":92,"journal-issue":{"issue":"1-3","published-print":{"date-parts":[[2007,6,13]]}},"URL":"https:\/\/doi.org\/10.1007\/s10540-007-9037-0","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6,13]]}}}