乳酸的直接线粒体进口支持弹性碳水化合物氧化
Ahmad A Cluntun1, Joseph R Visker2, Jesse N Velasco-Silva1
1Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
bioRxiv : the preprint server for biology
|October 17, 2024
概括
乳酸是一种能源,而不是废物. 单碳酸盐运输体1 (MCT1) 进口乳酸到心脏线粒体中进行氧化,在压力期间维持心脏功能,独立于线粒体的酸盐运输体 (MPC).
科学领域:
- 生物化学 生物化学
- 心脏病学 心脏病学
- 代谢过程中的代谢.
背景情况:
- 乳酸盐是一种高周转率的代谢物,越来越多地被认为是重要的能量来源.
- 传统上,人们认为,TCA循环中乳酸氧化成pyruvate仅发生在细胞质中,需要线粒体pyruvate载体 (MPC) 进口.
- 乳酸在心脏能量中的作用及其运输机制进入线粒体仍然是积极研究的领域.
研究的目的:
- 为了研究单碳酸盐载体1 (MCT1) 在心肌乳酸氧化中的作用.
- 为了确定乳酸是否可以在线粒体内氧化,独立于MPC.
- 阐明 MCT1 介导的乳酸代谢对压力下心脏功能的贡献.
主要方法:
- 在小鼠中利用C稳定同位素追踪与MPC的遗传删除.
- 隔离心脏线粒体以评估乳酸和酸盐代谢.
- 在压力条件下的野生类型和MCT1缺乏的小鼠中评估心脏功能和心力衰竭进展.
主要成果:
- 在小鼠心肌组织中证明了MPC独立的乳酸氧化.
- 确定了MCT1作为线粒体乳酸进口和氧化过程中的关键载体.
- 通过乳酸脱酶 (LDH) 的线粒体乳酸氧化产生NADH,支持呼吸和心脏功能,即使TCA循环受损.
- 在各种侮辱后,在缺乏心脏MCT1的小鼠中观察到心力衰竭的快速进展与减少的射出分数.
结论:
- 通过MCT1导入和氧化线粒体乳酸是维持心脏能量的一个重要途径.
- 这一途径允许碳水化合物进入TCA循环,并支持心肌结构和功能,特别是在压力下.
- 心脏特异性MCT1对于通过乳酸代谢维持能量供应来预防心力衰竭的进展至关重要.
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