奥菲奥博林A以表皮-介质细胞过渡 (EMT) 特定的方式影响线粒体氧化还原生物学
Haleigh N Parker1, Yongfeng Tao2, Jenna Tobin1
1Department of Biology, Baylor University, TX, Waco, USA.
Cancer cell international
|January 15, 2026
概括
奥菲奥博林A选择性地向侵袭性乳腺癌细胞中的线粒体,破坏新陈代谢并激活抗氧化防御. 这种天然化合物通过利用表皮细胞到介质细胞过渡 (EMT) 细胞的脆弱性来治疗转移性乳腺癌具有前途.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 表皮转移到介质细胞转移 (EMT) 驱动乳腺癌的进展,增加转移和耐药性.
- 奥菲奥博林A (OpA) 是一种由真菌衍生的类,具有强大的抗癌活性,但其点和机制尚不清楚.
- 了解OPA对EMT特征癌细胞的选择性作用对于治疗开发至关重要.
研究的目的:
- 阐明Ophiobolin A对EMT阳性乳腺癌细胞的选择性细胞毒性背后的分子机制.
- 确定OPA的分子标,并描述其对细胞代谢和生存途径的影响.
- 为了研究线粒体在OPA的作用机制中的作用.
主要方法:
- 使用了乳腺上皮和乳腺癌细胞系,具有和没有EMT特征.
- 采用质谱测量来识别与OPA相互作用的蛋白质,包括线粒体载体.
- 使用跨线粒体混合体来评估线粒体参与OpA敏感性.
- 分析了包括糖解,氧化代谢和TCA循环在内的代谢途径.
- 研究了NRF2-ARE抗氧化剂通路的激活.
主要成果:
- 确定了线粒体谷氨转运体SLC25A40作为EMT阳性细胞中的OPA相互作用蛋白.
- 证明线粒体调解细胞对OPA的敏感性.
- 透露的OPA破坏了糖解,氧化代谢和TCA循环代谢产物.
- 显示的OpA激活了EMT阳性细胞中的NRF2-ARE抗氧化途径.
- 在NRF2激活后证实了减少OpA细胞毒性.
结论:
- 奥菲奥博林A对EMT阳性乳腺癌细胞表现出线粒体介导的选择性.
- OpA诱导了导致细胞死亡的代谢转变,这种转变被激活的抗氧化机制抵消.
- OpA代表了一种潜在的治疗药物,准了侵袭性乳腺癌的代谢脆弱性.
更多相关视频
09:16Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry
Published on: February 3, 2023
2.9K
09:40Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
Published on: January 19, 2017
12.2K
相关概念视频
01:46Electron Transport Chain: Complex I and II
18.4K
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...
18.4K
01:45Mitochondrial Membranes
16.6K
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,...
16.6K
01:37Mitochondria
19.6K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
19.6K
01:19Translocation of Proteins into the Mitochondria
12.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
12.2K