线粒体复合体V的可逆解离能平衡癌症中对合成体和能量产生需求的平衡
Huabo Wang1, Jie Lu1, Colin Henchy1
1Division of Hematology/Oncology UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
iScience
|February 24, 2026
概括
癌细胞通过华堡效应重新编程新陈代谢,但线粒体ATP生成量下降. 一种新的机制涉及线粒体复合体V解离,平衡瘤生长的合成体前体.
科学领域:
- 生物化学 生物化学
- 癌症生物学 癌症生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 癌细胞表现出代谢重编程,包括华堡效应,以支持增殖.
- 瘤经常显示线粒体质量和氧化酸化的减少,从而产生合成醇-糖解质失衡.
- 在这种情况下,TCA循环在提供与糖解一起的合成体前体中的作用尚不清楚.
研究的目的:
- 为了研究癌细胞如何平衡增加的葡萄糖溶解衍生合成代谢物与TCA循环供应的前体.
- 阐明线粒体复合体V (CV) 在瘤代谢中的作用.
主要方法:
- 对原发性小鼠肝癌和衍生细胞系的分析.
- 研究线粒体复合体V (CV) 子单元的表达和组合.
- 评估线粒体膜潜力和ATP的产生.
主要成果:
- 线粒体复合体V (CV) 在癌细胞中分裂成独立的Fo和F1域.
- 降低MT-ATP6水平导致心血管解离,自由Fo作为质子孔,自由F1作为ATPase.
- 这种解离维持了线粒体膜的潜力,并调节了ATP水平,允许TCA循环的功能.
结论:
- 线粒体复合体V解离是平衡癌症中合成体前体供应的关键机制.
- 这个过程将TCA循环活动与ATP过度生产脱,支持瘤生长.
- 了解这种机制可以了解癌症代谢和潜在的治疗点.
相关概念视频
Electron Transport Chain: Complex I and II
19.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.2K
Adaptive Mechanisms in Cancer Cells
7.2K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.2K
Mitochondrial Membranes
17.5K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.5K
Muscle Recovery and Fatigue
4.5K
Muscle fatigue refers to the decline in a muscle's ability to maintain the force of contraction after prolonged activity. It primarily stems from changes within muscle fibers. Even before experiencing muscle fatigue, one may feel tired and have the urge to stop the activity. This response, known as central fatigue, occurs due to changes in the central nervous system, namely the brain and spinal cord. While there is no single mechanism that induces fatigue, it may serve as a protective...
4.5K
The Supercomplexes in the Crista Membrane
3.1K
The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
3.1K
Cancer Stem Cells and Tumor Maintenance
6.1K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
6.1K


