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瘤生长需要线粒体ubiquinol氧化

Inmaculada Martínez-Reyes¹, Luzivette Robles Cardona¹, Hyewon Kong¹

¹Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

|July 10, 2020

概括

瘤生长需要线粒体电子运输链 (ETC) 来氧化乌比奎诺,它为三碳酸 (TCA) 循环和胺合成提供燃料. 这一过程对于体内癌细胞的增殖至关重要.

科学领域:

生物化学
癌症生物学
线粒体生物学

背景情况:

线粒体电子运输链 (ETC) 对瘤生长和ATP生成至关重要.
功能性ETC在支持体内瘤进展中的确切作用尚不清楚.
线粒体对于人类大脑和肺部瘤中的葡萄糖氧化至关重要.

研究的目的:

阐明ETC支持瘤生长的具体机制.
调查基代谢及其下游癌症进展途径的必要性.
为了确定单独的NAD+再生是否足以在没有ETC复合体III的情况下促进瘤生长.

主要方法:

产生线粒体复合体III缺乏的癌细胞系.
使用Ciona intestinalis替代氧化酶 (AOX) 来挽救复合III缺乏症.
评估AOX表达细胞中的瘤生长,这些细胞缺乏I,II或二酸脱酶 (DHODH) 复合体.
评估表达Lactobacillus brevis NADH氧化酶 (LbNOX) 的细胞中的瘤生长以再生NAD+.

主要成果:

缺乏线粒体复合体III的癌细胞显示瘤生长受损.
通过AOX表达恢复了瘤生长,突出显示了ubiquinone的作用.
在AOX表达细胞中,I,II或DHODH复合体的丧失减少了瘤生长.
通过LbNOX的NAD+再生没有拯救复杂III缺乏细胞的瘤生长.

结论:

瘤生长需要ETC在氧化ubiquinol的功能.
乌比金氧化对于驱动氧化三酸循环和DHODH活性至关重要.
在体内,NAD+的再生不足以支持瘤的生长;在体内,ubiquinone的代谢是至关重要的.

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