Zhang Yinna, Lian Yajun, Lian Xiaolei, Zhang Haifeng, Chen Yuan, Sheng Hanqing, Feng Rui
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Neurochem Res. 2023 Jan;48(1):284-294. doi: 10.1007/s11064-022-03749-z. Epub 2022 Sep 12.
Mitophagy plays a key role in epileptic neuronal injury, and recent studies have shown that FUNDC1 plays an important role in regulating mitophagy. However, the specific effect of FUNDC1 on neuronal damage in epilepsy is unknown. In this study, we investigated the role of FUNDC1 in mitophagy and neuronal apoptosis using a hippocampal neuronal culture model of acquired epilepsy (AE) in vitro. We found that mitophagy levels were significantly increased in this model, as indicated by elevated LC3A/B ratios. FUNDC1 overexpression using lentiviral vectors enhanced mitophagy, whereas FUNDC1 down-regulation using lentiviral vectors impaired this process. Overexpression of FUNDC1 significantly decreased AE-induced superoxide anion, enhanced cell viability, reduced oxidative stress, and reduced neuronal apoptosis in epileptic hippocampus, while FUNDC1 down-regulation caused the opposite effect. In conclusion, we demonstrated that FUNDC1 is an important modulator of AE-induced neuronal apoptosis by controlling mitophagy function.
线粒体自噬在癫痫性神经元损伤中起关键作用,最近的研究表明,FUNDC1在调节线粒体自噬中起重要作用。然而,FUNDC1对癫痫中神经元损伤的具体作用尚不清楚。在本研究中,我们使用体外获得性癫痫(AE)的海马神经元培养模型,研究了FUNDC1在线粒体自噬和神经元凋亡中的作用。我们发现,该模型中线粒体自噬水平显著增加,如LC3A/B比率升高所示。使用慢病毒载体过表达FUNDC1可增强线粒体自噬,而使用慢病毒载体下调FUNDC1则会损害这一过程。FUNDC1的过表达显著降低了AE诱导的超氧阴离子,增强了细胞活力,降低了氧化应激,并减少了癫痫海马中的神经元凋亡,而FUNDC1的下调则产生相反的效果。总之,我们证明FUNDC1通过控制线粒体自噬功能是AE诱导的神经元凋亡的重要调节因子。