The role of mitochondrial aconitate (ACO2) in human sperm motility

The role of mitochondrial aconitate (ACO2) in human sperm motility
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DOI:
10.3109/19396368.2014.915360
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发表时间:
2014-10-01
影响因子:
2.4
通讯作者:
Yin, Chang-Jun
Yin, Chang-Jun
中科院分区:
医学3区
文献类型:
--
作者:
Tang, Min;Liu, Bian-Jiang;Yin, Chang-Jun

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三羧酸 (TCA) 循环酶的缺乏已被证明会导致多种人类疾病,包括恶性肿瘤、神经系统疾病和心脏病。在哺乳动物精子线粒体中,TCA 循环被认为是有助于产生 ATP 的重要代谢途径。线粒体顺乌头酸酶(ACO2)是 TCA 循环的重要调节酶,在弱精子症中的作用和机制目前知之甚少。在当前的研究中,免疫荧光染色将 ACO2 定位于人类精子的中段。通过免疫印迹,我们证明弱精子症样本中的 ACO2 蛋白水平与正常生育男性相比显着降低。重要的是,我们首先观察到异柠檬酸盐与低活力精子悬浮液的共孵育显着改善了精子活力,这可能是由于细胞内 ATP 升高所致。异柠檬酸盐改善精子活力可能对弱精子症的治疗具有重要的临床意义,当然值得进一步研究。
Deficiencies in tricarboxylic acid (TCA) cycle enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. In mammalian spermatozoa mitochondria, the TCA cycle is known to be a crucial metabolic pathway that contributes to produce ATP. There is little known about the role and mechanism of mitochondrial aconitase (ACO2), which is an important regulatory enzyme of the TCA cycle, in asthenozoospermia. In the current study, immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men. Importantly, we first observed that co-incubation of isocitrate with low motile sperm suspensions significantly improved sperm motility, which might be due to elevated intracellular ATP. The improvement of the sperm motility by isocitrate may have important clinical implications in the treatment of asthenozoospermia and certainly warrants further investigation.