"ATAD3C调节了线粒体膜中的ATAD3A组合和功能"
Paula Gaudó1, Elena de Tomás-Mateo1, Nuria Garrido-Pérez2
1Biochemistry and Molecular Biology Department. Universidad de Zaragoza, 50009- and 50013, Zaragoza, Spain.
Free radical biology & medicine
|December 13, 2023
概括
以前认为不活跃的ATAD3C蛋白现在被证明可以负面调节线粒体功能. 它被纳入ATAD3A复合体会损害细胞增殖和氧气消耗,影响线粒体组织.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞生物化学 细胞生物化学
- 遗传学 遗传学 是一个
背景情况:
- 含有酶ATAD3A的线粒体ATPase与多种细胞活动 (AAA) 相关的域对内线粒体膜组织至关重要,并与儿童疾病有关.
- 人类进化导致了ATAD3A对应物:ATAD3B和ATAD3C,而ATAD3C在很大程度上被认为是一种假基因.
研究的目的:
- 为了研究细胞活动和ATAD3C对比的功能作用.
- 确定ATAD3C对线粒体结构和功能的影响,特别是与ATAD3A有关的影响.
主要方法:
- 在HEK 293T细胞和人体组织中检测ATAD3C.
- ATAD3C作为一个不可分割的膜蛋白质的表征.
- 在纤维细胞中进行过度表达研究,以评估对细胞增殖,氧气消耗和反应性氧物种 (ROS) 生产的影响.
- ATAD3A复合体大小和呼吸链组件的分析.
主要成果:
- ATAD3C在细胞和组织中表达,并作为一个不可分割的膜蛋白质起作用.
- 与ATAD3A不同的是,ATAD3C的过度表达减少了细胞增殖和氧气消耗,同时增加了ROS.
- ATAD3C单体纳入ATAD3A复合体,减少其大小并改变线粒体膜组织.
- ATAD3C表达促进了二维CIII在内膜中的积累,阻碍了超复杂的形成.
结论:
- ATAD3C表现出负面的主导作用,调节线粒体膜中的ATAD3A功能.
- ATAD3C影响线粒体氧化酸化 (OXPHOS) 和细胞能量代谢.
- 这些发现表明,ATAD3C在线粒体功能中起着重要的调节作用,挑战其伪基地位.
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