单个线粒体ATP分析直接发现了癌症中可向的OXPHOS依赖性
Xu Xiao1, Cheng Lu1, Hao Chen1
1Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Fujian Key Laboratory of Chemical Biology (Xiamen University), State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 13, 2026
概括
癌细胞表现出比正常细胞更高的线粒体ATP水平,这是通过一种新的纳米流细胞计方法揭示的. 这个平台通过选线粒体代谢抑制剂来帮助开发向疗法.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 线粒体腺三酸盐 (mitoATP) 对癌细胞能量至关重要,但其测量是困难的.
- 癌细胞通常依赖于氧化酸化 (OXPHOS),与华堡效应相反.
- 线粒体异质性和细胞干扰复杂化了有机细胞水平的ATP量化.
研究的目的:
- 开发一种用于单个线粒体ATP测量的新平台.
- 为了量化癌症与正常细胞中的mitoATP水平.
- 建立癌症选择性线粒体代谢抑制剂的查策略.
主要方法:
- 开发了MitoATP-nFCM,这是一个纳米流细胞测量平台,用于单个线粒体的ATP测量.
- 使用了同时的光和侧向散射检测.
- 分析了ATP水平,膜潜力,ATP合成酶,基酶2和选的抑制剂.
主要成果:
- 通过MitoATP-nFCM,可以精确量化单个有机细胞的ATP.
- 癌细胞线粒体的ATP水平比正常细胞高1.7-1.9倍.
- 确定了特定的OXPHOS抑制剂:贝达基林,VLX600和CPI-613.
结论:
- 线粒体ATP-nFCM是癌症中线粒体生物能学的分析的一个有价值的工具.
- 癌细胞表现出一种OXPHOS主导的表型,具有重编程的线粒体代谢.
- 该平台有助于精确选用于癌症治疗的新型线粒体代谢抑制剂.
相关概念视频
ATP Yield
79.2K
Cellular respiration produces 30 - 32 ATP per glucose molecule. Although most of the ATP results from oxidative phosphorylation and the electron transport chain (ETC), 4 ATP are gained beforehand (2 from glycolysis and 2 from the citric acid cycle).
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
79.2K
Hydrolysis of ATP
82.0K
The bonds of adenosine triphosphate (ATP) can be broken through the addition of water, releasing one or two phosphate groups in an exergonic process called hydrolysis. This reaction liberates the energy in the bonds for use in the cell—for instance, to synthesize proteins from amino acids.
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine...
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine...
82.0K
Targeted Cancer Therapies
9.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
9.0K
Drug Discovery: Overview
11.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
11.9K
ATP Synthase: Mechanism
17.3K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
17.3K
ATP and Energy Production
2.0K
Adenosine triphosphate (ATP) is a critical molecule that functions as the main energy carrier in cells. Structurally, ATP consists of an adenosine molecule—comprising adenine and ribose—bonded to three phosphate groups. The high-energy bonds between these phosphate groups store significant amounts of potential energy. This energy is released during hydrolysis, wherein ATP is converted to adenosine diphosphate (ADP) or adenosine monophosphate (AMP), driving a variety of essential...
2.0K


