替代性酶载体缺乏多个广泛分布的基因,这些基因编码了外围的OXPHOS子单元
Murilo F Othonicar1, Geovana S Garcia1, Marcos T Oliveira1
1Departamento de Biotecnologia, Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal, Universidade Estadual Paulista "Júlio de Mesquita Filho", Jaboticabal, SP, Brazil.
Biochimica et biophysica acta. Bioenergetics
|April 20, 2024
概括
化替代酶 (AE) NDX和AOX显示了线粒体疾病治疗的潜力. 它们的独特进化表明它们的功能不同,可能没有超级复杂,这影响了它们在人类旁路治疗中的使用.
科学领域:
- 线粒体呼吸 线粒体呼吸
- 进化生物学是进化的生物学.
- 生物化学 生物化学
背景情况:
- 来自Ciona intestinalis的替代酶 (AE) NDX和AOX为线粒体疾病的绕道疗法提供了潜在的潜力.
- 这些AE在脊椎动物和昆虫中不存在,这促使人们对长袍呼吸链的组成进行了调查.
- 线粒体疾病是由呼吸链复合体I,III和IV的缺陷引起的.
研究的目的:
- 为了研究状呼吸链的独特组成及其替代酶 (AE) 的安置.
- 评估Ciona AEs与异质系统中的辅酶Q池的功能相互作用.
- 评估Ciona AEs对人类线粒体疾病的旁路疗法的适用性.
主要方法:
- 在人类细胞,Drosophila melanogaster和小鼠中,Ciona NDX和AOX的异种表达和表征.
- 对衣动物基因组的生物信息分析,以确定正统的呼吸链子单元.
- 锡奥纳呼吸链多的结构建模.
- 使用Drosophila表达的Ciona AOX进行功能性测试,以确定辅酶Q池的可访问性.
主要成果:
- 哺乳动物中复杂相互作用和超复杂物 (SCs) 关键的15个正统的呼吸链子单元基因在形动物的基因组中缺席.
- 结构建模揭示了Ciona呼吸链子单元的显著分歧,与这些正义词的缺失一致.
- 当表达为Drosophila时,Ciona AOX无法访问由复合物I减少的辅酶Q,但可以通过糖酸盐氧化酶 (非SC脱酶) 氧化辅酶Q.
结论:
- 锡奥纳AE可能是在一个独特的线粒体内膜环境中演变的,可能缺乏超级复杂物 (SC).
- 在异质系统中,Ciona AEs与非SC脱酶的功能相互作用支持它们独特的进化路径.
- 这些发现影响了对动物呼吸链演化的理解,以及Ciona AEs在人类线粒体疾病治疗中的潜在应用.
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