Altered mitochondrial acetylation profiles in a kainic acid model of temporal lobe epilepsy

Free Radical Biology & Medicine
Lindsey B GanoManisha Patel

Abstract

Impaired bioenergetics and oxidative damage in the mitochondria are implicated in the etiology of temporal lobe epilepsy, and hyperacetylation of mitochondrial proteins has recently emerged as a critical negative regulator of mitochondrial functions. However, the roles of mitochondrial acetylation and activity of the primary mitochondrial deacetylase, SIRT3, have not been explored in acquired epilepsy. We investigated changes in mitochondrial acetylation and SIRT3 activity in the development of chronic epilepsy in the kainic acid rat model of TLE. Hippocampal measurements were made at 48 h, 1 week and 12 weeks corresponding to the acute, latent and chronic stages of epileptogenesis. Assessment of hippocampal bioenergetics demonstrated a ≥ 27% decrease in the ATP/ADP ratio at all phases of epileptogenesis (p < 0.05), whereas cellular NAD+ levels were decreased by ≥ 41% in the acute and latent time points (p < 0.05), but not in chronically epileptic rats. In spontaneously epileptic rats, we found decreased protein expression of SIRT3 and a 60% increase in global mitochondrial acetylation, as well as enhanced acetylation of the known SIRT3 substrates MnSOD, Ndufa9 of Complex I and IDH2 (all p < 0.05), suggesting SIRT3 dysfunction ...Continue Reading

Citations

Nov 22, 2018·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Maria Elisa SerranoAlain Plenevaux
May 29, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Huimin KongQiang Luo
Jan 26, 2021·Frontiers in Molecular Neuroscience·Amanda M do CantoIscia Lopes-Cendes
Dec 11, 2020·Oxidative Medicine and Cellular Longevity·Nan YangXiao-Yuan Mao
Mar 17, 2021·Seizure : the Journal of the British Epilepsy Association·Estela M BruxelIscia Lopes-Cendes
Mar 30, 2021·Mitochondrion·Shareen SinghRupinder Kaur
May 25, 2021·Epilepsy Currents·Alisha Aroor, Amy L Brewster
Oct 20, 2021·Frontiers in Neurology·Ya-Wen XuDe-Zhi Kang

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