title: Mitochondrial dysfunction and seizures: the neuronal energy crisis.
abstract: Seizures are often the key manifestation of neurological diseases caused by pathogenic mutations in 169 of the genes that have so far been identified to affect mitochondrial function. Mitochondria are the main producers of ATP needed for normal electrical activities of neurons and synaptic transmission. Additionally, they have a central role in neurotransmitter synthesis, calcium homoeostasis, redox signalling, production and modulation of reactive oxygen species, and neuronal death. Hypotheses link mitochondrial failure to seizure generation through changes in calcium homoeostasis, oxidation of ion channels and neurotransmitter transporters by reactive oxygen species, a decrease in neuronal plasma membrane potential, and reduced network inhibition due to interneuronal dysfunction. Seizures, irrespective of their origin, represent an excessive acute energy demand in the brain. Accordingly, secondary mitochondrial dysfunction has been described in various epileptic disorders, including disorders that are mainly of non-mitochondrial origin. An understanding of the reciprocal relation between mitochondrial dysfunction and epilepsy is crucial to select appropriate anticonvulsant treatment and has the potential to open up new therapeutic approaches in the subset of epileptic disorders caused by mitochondrial dysfunction.
authors: Division of Neurochemistry, Department of Epileptology, and Life & Brain Center, University of Bonn, Bonn, Germany.
authors: Gábor
authors: G
authors: Zsurka
authors: Division of Neurochemistry, Department of Epileptology, and Life & Brain Center, University of Bonn, Bonn, Germany. Electronic address: wolfram.kunz@ukb.uni-bonn.de.
authors: Wolfram S
authors: WS
authors: Kunz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D012640:Seizures / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology