Skip to main content
SpringerLink
Log in

Mitochondriale Fehlfunktion und Anfälle: die neuronale Energiekrise

Mitochondrial dysfunction and seizures: the neural energy crisis

  • Leitthema
  • Published:
Zeitschrift für Epileptologie Aims and scope Submit manuscript

Zusammenfassung

Anfälle sind häufig die Hauptmanifestation von neurologischen Erkrankungen durch Mutationen in bisher 169 Genen, die die mitochondriale Funktion beeinflussen. Mitochondrien sind die Hauptproduzenten des ATP, das für die normale neuronale Aktivität und die synaptische Transmission benötigt wird. Gegenwärtige Hypothesen verknüpfen mitochondriale Dysfunktion und Anfälle mit einer Änderung der Calciumhomöostase, der ROS (reaktiven Sauerstoffspecies)-abhängigen Oxidation von Ionenkanälen und Rezeptoren, der Reduktion des neuronalen Membranpotenzials sowie einer verringerten Netzwerkhemmung durch Fehlfunktion von Interneuronen.

Abstract

Seizures are often the key manifestation of neurological diseases caused by pathogenic mutations in presently 169 genes affecting mitochondrial function. Mitochondria are the main producers of ATP required for normal neuronal electric activity and synaptic transmission. Current hypotheses link mitochondrial failure to seizure generation through alterations of calcium homeostasis, ROS (reactive oxygen species)-induced oxidation of ion channels and neurotransmitter transporters, reduction of neuronal plasma membrane potential, and reduced network inhibition due to interneuronal dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Hirano M, Kunz WS, DiMauro S (2008) Mitochondrial diseases. In: Engel J, Pedley TA (Hrsg) Epilepsy – A comprehensive textbook, Bd. 3. Lippincott Williams & Wilkins, Philadelphia, S 2621–2630

    Google Scholar 

  2. Zsurka G, Kunz WS (2015) Mitochondrial dysfunction and seizures: the neuronal energy crisis. Lancet Neurol 14:956–966

    Article  CAS  PubMed  Google Scholar 

  3. Kann O, Kovacs R, Njunting M, Behrens CJ, Otahal J, Lehmann TN, Gabriel S, Heinemann U (2005) Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain 128:2396–2407

    Article  PubMed  Google Scholar 

  4. Kunz WS, Kudin AP, Vielhaber S, Blümcke I, Zuschratter W, Schramm J, Beck H, Elger CE (2000) Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy. Ann Neurol 48:766–773

    Article  CAS  PubMed  Google Scholar 

  5. Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61:931–937

    Article  CAS  PubMed  Google Scholar 

  6. Cock H, Schapira AHV (1999) Mitochondrial DNA mutations and mitochondrial dysfunction in epilepsy. Epilepsia 40(Suppl. 3):33–40

    Article  CAS  PubMed  Google Scholar 

  7. Naviaux RK, Nguyen KV (2004) POLG mutations associated with Alpers’ syndrome and mitochondrial DNA depletion. Ann Neurol 55:706–712

    Article  CAS  PubMed  Google Scholar 

  8. Zsurka G, Baron M, Stewart JD, Kornblum C, Bös M, Sassen R, Taylor RW, Elger CE, Chinnery PF, Kunz WS (2008) Clonally expanded mitochondrial DNA mutations in epileptic individuals with mutated DNA polymerase gamma. J Neuropathol Exp Neurol 67:857–866

    Article  CAS  PubMed  Google Scholar 

  9. Hallmann K, Zsurka G, Moskau-Hartmann S, Kirschner J, Korinthenberg R, Ruppert AK, Ozdemir O, Weber Y, Becker F, Lerche H, Elger CE, Thiele H, Nürnberg P, Sander T, Kunz WS (2014) A homozygous splice-site mutation in CARS2 is associated with progressive myoclonic epilepsy. Neurology 83:2183–2187

    Article  CAS  PubMed  Google Scholar 

  10. Vielhaber S, von Oertzen JH, Kudin AP, Schoenfeld A, Menzel C, Biersack HJ, Kral T, Elger CE, Kunz WS (2003) Correlation of hippocampal glucose oxidation capacity and interictal FDG-PET in temporal lobe epilepsy. Epilepsia 44:193–199

    Article  CAS  PubMed  Google Scholar 

  11. 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) Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy. Epilepsia 49:40–50

    Article  CAS  PubMed  Google Scholar 

  12. Otáhal J, Folbergrová J, Kovacs R, Kunz WS, Maggio N (2014) Epileptic focus and alteration of metabolism. Int Rev Neurobiol 114:209–243

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Epileptologie, Abteilung Neurochemie, LIFE & BRAIN Center, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland

    Wolfram S. Kunz

Authors
  1. Wolfram S. Kunz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfram S. Kunz.

Ethics declarations

Interessenkonflikt

W. S. Kunz gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kunz, W.S. Mitochondriale Fehlfunktion und Anfälle: die neuronale Energiekrise. Z. Epileptol. 29, 84–86 (2016). https://doi.org/10.1007/s10309-015-0036-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10309-015-0036-z

Schlüsselwörter

Keywords

Search

Navigation