INMED-INSERM U901, Parc Scientifique de Luminy, 13273, Marseille, cedex 09, France.
J Bioenerg Biomembr. 2010 Dec;42(6):467-71. doi: 10.1007/s10863-010-9323-6.
The mitochondrion is a key cellular structure involved in many metabolic functions such as ATP synthesis by oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation. These pathways are fundamental for biological processes such as cell proliferation or death. In the central nervous system, mitochondria dysfunctions have been involved in many neurological diseases and age-related neurodegenerative disorders, including epilepsy, Alzheimer's and Parkinson's diseases. Mitochondrial diseases are frequently caused by a disruption of the respiratory chain. Nevertheless, other mitochondrial functions, including organellar dynamics or metabolite transport, could also be involved in such pathologies. Here we described mitochondrial dysfunctions in a very severe, intractable and relatively rare neonatal epileptic encephalopathy, the Ohtahara syndrome. This condition is characterized by neonatal onset of seizures, interictal electroencephalogram with suppression burst pattern and a very poor outcome with very severe psychomotor retardation or death. The etiology of this disease remains elusive but seems to be very heterogeneous including brain malformations, metabolic errors, transcription factor and synaptic vesicle release defects. In this review, we discuss first the Ohtahara syndrome caused by mitochondrial respiratory chain damages, suggesting that these defects could be more common than previously thought. Then, we will adress the importance of the mitochondrial glutamate carrier SLC25A22 in these pathologies, since mutations of this gene were described in two distinct families. These findings suggest that glutamate metabolism should also be considered as an important cause of the Ohtahara syndrome.
线粒体是一种参与许多代谢功能的关键细胞结构，例如通过氧化磷酸化、三羧酸循环或脂肪酸氧化合成 ATP。这些途径是细胞增殖或死亡等生物过程的基础。在中枢神经系统中，线粒体功能障碍与许多神经疾病和与年龄相关的神经退行性疾病有关，包括癫痫、阿尔茨海默病和帕金森病。线粒体疾病通常是由呼吸链的破坏引起的。然而，其他线粒体功能，包括细胞器动力学或代谢物运输，也可能与这些病理有关。在这里，我们描述了一种非常严重、难治且相对罕见的新生儿癫痫性脑病——大田原综合征中的线粒体功能障碍。这种情况的特征是新生儿发作、发作间期脑电图呈抑制爆发模式，以及严重的精神运动发育迟缓和死亡等非常差的预后。这种疾病的病因仍然难以捉摸，但似乎非常多样化，包括脑畸形、代谢错误、转录因子和突触囊泡释放缺陷。在这篇综述中，我们首先讨论了由线粒体呼吸链损伤引起的大田原综合征，表明这些缺陷可能比以前认为的更常见。然后，我们将讨论线粒体谷氨酸载体 SLC25A22 在这些疾病中的重要性，因为该基因的突变在两个不同的家族中都有描述。这些发现表明，谷氨酸代谢也应被视为大田原综合征的一个重要原因。
