Abstract
A broad variety of mutations of the mitochondrial DNA or nuclear genes that lead to the impairment of mitochondrial respiratory chain or mitochondrial ATP synthesis have been associated with epileptic phenotypes. Additionally, evidence for an impaired mitochondrial function in seizure focus of patients with temporal lobe epilepsy and Ammon’s horn sclerosis, as well as, animal models of temporal lobe epilepsy has been accumulated. This implies a direct pathogenic role of mitochondrial dysfunction in the process of epileptogenesis and seizure generation in certain forms of epilepsy.
Similar content being viewed by others
References
Baron M, Kudin AP, Kunz WS (2007) Biochem Soc Trans 35:1228–1231
Bataillard M, Chatzoglou E, Rumbach L, Sternberg D, Tournade A, Lafort P, Jardel C, Maisonobe T, Lombes A (2001) Neurology 56, 405–407
Bindokas VP, Lee CC, Colmers WF, Miller RJ (1998) J Neurosci 18:4570–4587
Blümcke I, Zuschratter W, Schewe JC, Suter B, Lie AA, Riederer BM, Meier B, Schramm J, Elger CE, Wiestler OD (1999) J Comp Neurol 414:437–453
Brini M, Pinton P, King MP, Davidson M, Schon EA, Rizutto R (1999) Nat Med 5:951–954
Brown MD, Zhadanov S, Allen JC, Hosseini S, Newman NJ, Atamonov VV, Mikhailovskaya IE, Sukernik RI, Wallace DC (2001) Hum Genet 109:33–39
Campos Y, Lorenzo G, Martin MA, Torregrosa A, del Hoyo P, Rubio JC, Garcia A, Arenas J (2000) Neuromuscul Disord 10:493–496
Canafoglia L, Franceschetti S, Antozzi C, Carrara F, Farina L, Granata T, Lamantea E, Savoiardo M, Uziel G, Villani F, Zeviani M, Avanzini G (2001) Neurology 56:1340–1346
Cock H, Schapira AHV (1999) Epilepsia 40(suppl 3):33–40
De Coo IF, Renier WO, Ruitenbeek W, Ter Laak HJ, Bakker M, Schägger H, Van Oost BA, Smeets HJ (1999) Ann Neurol 45:130–133
De Vries DD, van Engelen BG, Gabrels FJ, Ruitenbeek W, van Oost BA (1993) Ann Neurol 34:410–412
Frantseva MV, Velazquez JL, Hwang PA, Carlen PL (2000) Eur J Neurosci 12:1431–1439
Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653
Goto Y, Nonaka I, Horai S (1991) Biochim Biophys Acta 1097:238–240
Goto Y, Tsugane K, Tanabe Y, Nonaka I, Horai S (1994) Biochem Biophys Res Commun 202:1624–1630
Gulyás AI, Buzsáki G, Freund TF, Hirase H (2006) Eur J Neurosci 23:2581–2594
Guo X, Popadin KY, Markuzon N, Orlov YL, Kraytsberg Y, Krishnan KJ, Zsurka G, Turnbull DM, Kunz WS, Khrapko K (2010) Trends Genet 26:340–343
Hanna MG, Nelson IP, Morgan-Hughes JA, Wood NW (1998) J Neurol Neurosurg Psychiatry 65:512–517
Hirano M, Kunz WS, DiMauro S (2008) In epilepsy—a comprehensive textbook: mitochondrial diseases. In: Engel J, Pedley TA (eds) Lippincott Williams & Wilkins, Philadelphia, Vol. III, pp 2621–2630
Jaksch M, Klopstock T, Kurlemann G, Dörner M, Hofmann S, Kleinle S, Hegemann S, Weissert M, Müller-Höcker J, Pongratz D, Gerbitz KD (1998) Ann Neurol 44:635–640
Kann O, Schuchmann S, Buchheim K, Heinemann U (2003) Neuroscience 119:87–100
Kann O, Kovács R, Njunting M, Behrens CJ, Otahal J, Lehmann TN, Gabriel S, Heinemann U (2005) Brain 128:2396–2407
Kovács R, Schuchmann S, Gabriel S, Kann O, Kardos J, Heinemann U (2002) J Neurophysiol 88:2909–2918
Kudin AP, Kudina TA, Seyfried J, Vielhaber S, Beck H, Elger CE, Kunz WS (2002) Eur J Neurosci 15:1105–1114
Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) J Biol Chem 279:4127–4135
Kudin AP, Malinska D, Kunz WS (2008) Biochim Biophys Acta 1777:689–695
Kudin AP, Zsurka G, Elger CE, Kunz WS (2009) Exp Neurol 218:326–332
Kunz WS (2002) The role of mitochondria in epileptogenesis. Curr Opin Neurol 15:179–184
Kunz WS, Goussakov IV, Beck H, Elger CE (1999) Brain Res 826:236–242
Kunz WS, Kudin AP, Vielhaber S, Blümcke I, Zuschratter W, Schramm J, Beck H, Elger CE (2000) Ann Neurol 48:766–773
Krajewski S, Krajewska M, Ellerby LM, Welsh K, Xie Z, Deveraux QL, Salvesen GS, Bredesen DE, Rosenthal RE, Fiskum G, Reed JC (1999) Proc Natl Acad Sci USA 96:5752–5757
Liang LP, Ho YS, Patel M (2000) Neuroscience 101:563–570
Malinska D, Kulawiak B, Kudin AP, Kovács R, Huchzermeyer C, Kann O, Szewczyk A, Kunz WS (2010) Biochim Biophys Acta 1797:1163–1170
Mancuso M, Filosto M, Mootha VK, Rocchi A, Pistolesi S, Murri L, DiMauro S, Siciliano G (2004) Neurology 62:2119–2121
Manfredi G, Schon EA, Moraes CT, Bonilla E, Berry GT, Sladky JT, DiMauro S (1995) Neuromuscul Disord 5:391–398
Manfredi G, Schon EA, Bonilla E, Moraes CT, Shanske S, DiMauro S (1996) Hum Mutat 7:158–163
Moraes CT, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N, Lovelace RE, Rowland LP, Schon EA, DiMauro S (1993) J Clin Invest 92:2906–2915
Morten KJ, Cooper JM, Brown GK, Lake BD, Pike D, Poulton J (1993) Hum Mol Genet 2:2081–2087
Naini AB, Lu J, Kaufmann P, Bernstein RA, Mancuso M, Bonilla E, Hirano M, DiMauro S (2005) Arch Neurol 62:473–476
Naviaux RK, Nguyen KV (2004) Ann Neurol 55:706–712
Nishigaki Y, Tadesse S, Bonilla E, Shungu D, Hersh S, Keats BJ, Berlin CI, Goldberg MF, Vockley J, DiMauro S, Hirano M (2003) Neuromuscul Disord 13:334–340
Nishino I, Komatsu M, Kodama S, Horai S, Nonaka I, Goto Y (1996) The 3260 mutation in mitochondrial DNA can cause mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Muscle Nerve 19:1603–1604
O’Brien TJ, Newton MR, Cook MJ, Berlangieri SU, Kilpatrick C, Morris K, Berkovic SF (1997) Epilepsia 38:74–80
Pulkes T, Liolitsa D, Eunson LH, Rose M, Nelson IP, Rahman S, Poulton J, Marchington DR, Landon DN, Debono AG, Morgan-Hughes JA, Hanna MG (2005) Neuromuscul Disord 15:364–371
Ravn K, Wibrand F, Hansen FJ, Horn N, Rosenberg T, Schwartz M (2001) Eur J Hum Genet 9:805–809
Sakuta R, Nonaka I (1989) Vascular involvement in mitochondrial myopathy. Ann Neurol 25:594–601
Santorelli FM, Mak SC, Vazquez-Acevedo M, Gonzlez-Halphen D, DiMauro S (1995) Biochem Biophys Res Commun 216:835–840
Santorelli FM, Tanji K, Kulikova R, Shanske S, Vilarinho L, Hays AP, DiMauro S (1997) Biochem Biophys Res Commun 238:326–328
Sato W, Hayasaka K, Shoji Y, Takahashi T, Takada G, Saito M, Fukawa O, Wachi E (1994) Biochem Mol Biol Int 33:1055–1061
Schröder R, Vielhaber S, Wiedemann FR, Kornblum C, Papassotiropoulos A, Broich P, Zierz S, Elger CE, Reichmann H, Seibel P, Klockgether T, Kunz WS (2000) J Neuropath Exp Neurol 59:353–360
Schuchmann S, Albrecht D, Heinemann U, von Bohlen und Halbach O (2002) Neurobiol Dis 11:96–105
Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (1990) Cell 61:931–937
Shtilbans A, El-Schahawi M, Malkin E, Shanske S, Musumeci O, DiMauro S (1999) J Child Neurol 14:610–613
Shtilbans A, Shanske S, Goodman S, Sue CM, Bruno C, Johnson TL, Lava NS, Waheed N, DiMauro S (2000) J Child Neurol 15:759–761
Suomalainen A, Majander A, Wallin M, Setälä K, Kontula K, Leinonen H, Salmi T, Paetau A, Haltia M, Valanne L, Lonnqvist J, Peltonen L, Somer H (1997) Neurology 48:1244–1253
Taniike M, Fukushima H, Yanagihara I, Tsukamoto H, Tanaka J, Fujimura H, Nagai T, Sano T, Yamaoka K, Inui K (1992) Biochem Biophys Res Commun 186:47–53
Tang YG, Zucker RS (1997) Neuron 18:483–491
Taylor RW, Chinnery PF, Haldane F, Morris AA, Bindoff LA, Wilson J, Turnbull DM (1996) Ann Neurol 40:459–462
Taylor RW, Singh-Kler R, Hayes CM, Smith PE, Turnbull DM (2001) Ann Neurol 50:104–107
Taylor RW, Schaefer AM, McDonnell MT, Petty RK, Thomas AM, Blakely EL, Hayes CM, McFarland R, Turnbull DM (2004) Neurology 62:1420–1423
Tiranti V, Carrara F, Confalonieri P, Mora M, Maffei RM, Lamantea E, Zeviani M (1999) Neuromuscul Disord 9:66–71
Van Goethem G, Dermaut B, Löfgren A, Martin JJ, Van Broeckhoven C (2001) Nat Genet 28:211–212
Varlamov DA, Kudin AP, Vielhaber S, Schröder R, Sassen R, Becker A, Kunz D, Haug K, Rebstock J, Heils A, Elger CE, Kunz WS (2002) Hum Mol Genet 11:1797–1805
Vielhaber S, von Oertzen JH, Kudin AP, Schoenfeld A, Menzel C, Biersack HJ, Kral T, Elger CE, Kunz WS (2003a) Epilepsia 44:193–199
Vielhaber S, Kudin AP, Kudina TA, Stiller D, Scheich H, Schoenfeld A, Feistner H, Heinze HJ, Elger CE, Kunz WS (2003b) Eur J Neurosci 18:2292–2230
Vielhaber S, Niessen HG, Debska-Vielhaber G, Kudin AP, Wellmer J, Kaufmann J, Schönfeld MA, Fendrich R, Willker W, Leibfritz D, Schramm J, Elger CE, Heinze HJ, Kunz WS (2008) Epilepsia 49:40–50
Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM, Engelsen BA, Moen G, Bindoff LA (2005) Neurology 64:1204–1208
Wulff P, Ponomarenko AA, Bartos M, Korotkova TM, Fuchs EC, Bähner F, Both M, Tort AB, Kopell NJ, Wisden W, Monyer H (2009) Proc Natl Acad Sci USA 106:3561–3566
Zeviani M, Muntoni F, Savarese N, Serra G, Tiranti V, Carrara F, Mariotti C, DiDonato S (1993) Eur J Hum Genet 1:80–87
Zsurka G, Baron M, Stewart JD, Kornblum C, Bös M, Sassen R, Taylor RW, Elger CE, Chinnery PF, Kunz WS (2008) J Neuropathol Exp Neurol 67:857–866
Zsurka G, Hampel KG, Nelson I, Jardel C, Mirandola SR, Sassen R, Kornblum C, Marcorelles P, Lavoué S, Lombès A, Kunz WS (2010) Neurology 74:507–512
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zsurka, G., Kunz, W.S. Mitochondrial dysfunction in neurological disorders with epileptic phenotypes. J Bioenerg Biomembr 42, 443–448 (2010). https://doi.org/10.1007/s10863-010-9314-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10863-010-9314-7