title: Association of mitochondrial letm1 with epileptic seizures.
abstract: Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial protein that is associated with seizure attacks in Wolf-Hirschhorn syndrome. This study aimed to investigate the expression pattern of Letm1 in patients with temporal lobe epilepsy (TLE) and pilocarpine-induced rat model of epilepsy, and to determine if altered Letm1 leads to mitochondrial dysfunction and increased susceptibility to seizures. Using immunohistochemical, immunofluorescent, western blotting, and transmission electron microscopic methods, we have found that Letm1 was significantly decreased in TLE patients, and gradually decreased in experimental rats from 1 to 7 days after onset of seizures. Letm1 knock-down by a lentivirus bearing LV-Letm1-sh resulted in mitochondrial swelling and decreased expression of Letm1 target protein mitochondrially encoded cytochrome B (MT-CYB). Behavioral study revealed that inhibition of Letm1 caused early onset of the first seizure, increased seizure frequency, and duration. However, administration of Letm1 homolog nigericin failed to prevent epilepsy. These results indicate that inhibition of Letm1 and mitochondrial dysfunctions contributes to the development of epileptic seizures. Appropriate Letm1 level may be critical for maintaining normal neuronal functions.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and Department of Neurology, The Third People's Hospital of Chongqing, Chongqing 400014, China.
authors: Xiaogang
authors: X
authors: Zhang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Guojun
authors: G
authors: Chen
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Yaodong
authors: Y
authors: Lu
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Jing
authors: J
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Min
authors: M
authors: Fang
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Jing
authors: J
authors: Luo
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Qingqing
authors: Q
authors: Cao
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing 400016, China and.
authors: Xuefeng
authors: X
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C488528:LETM1 protein, human; C000594751:LETM1 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010862:Pilocarpine
keywords: Letm1; MT-CYB; lentivirus; mitochondria; temporal lobe epilepsy