Reviving mitochondrial bioenergetics: A relevant approach in epilepsy

Shareen Singh, Thakur Gurjeet Singh, Ashish Kumar Rehni, Vivek Sharma, Manjinder Singh, Rupinder Kaur

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Epileptogenesis is most commonly associated with neurodegeneration and a bioenergetic defect attributing to the fact that mitochondrial dysfunction plays a key precursor for neuronal death. Mitochondria are the essential organelle of neuronal cells necessary for certain neurophysiological processes like neuronal action potential activity and synaptic transmission. The mitochondrial dysfunction disrupts calcium homeostasis leading to inhibitory interneuron dysfunction and increasing the excitatory postsynaptic potential. In epilepsy, the prolonged repetitive neuronal activity increases the excessive demand for energy and acidosis in the brain further increasing the intracellular calcium causing neuronal death. Similarly, the mitochondrial damage also leads to the decline of energy by dysfunction of the electron transport chain and abnormal production of the ROS triggering the apoptotic neuronal death. Thus, the elevated level of cytosolic calcium causes the mitochondria DNA damage coinciding with mtROS and releasing the cytochrome c binding to Apaf protein further initiating the apoptosis resulting in epileptic encephalopathies. The various genetic and mRNA studies of epilepsy have explored the various pathogenic mutations of genes affecting the mitochondria functioning further initiating the neuronal excitotoxicity. Based on the results of previous studies, the recent therapeutic approaches are targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria and hold great promise to attenuate epileptogenesis. Therefore, the current review emphasizes the emerging insights to uncover the relation between mitochondrial dysfunction and ROS generation contributing to mechanisms underlying epileptic seizures.

Original languageEnglish (US)
Pages (from-to)213-226
Number of pages14
JournalMitochondrion
Volume58
DOIs
StatePublished - May 2021

Keywords

  • Calcium homeostasis
  • Epilepsy
  • Mitochondrial dysfunction
  • Neurodegeneration
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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