相关实验视频

Updated: Jul 9, 2025

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Author Spotlight: Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

线粒体的NADH穿系统是3组髓母细胞瘤在低氧微环境中的可准的漏洞

J Contenti^1,2, Y Guo³, A Mazzu³

¹Université Côte d'Azur, INSERM U1065, C3M, 151 Route de St Antoine de Ginestière, BP2 3194, CEDEX 03, 06204, Nice, France. contenti.j@chu-nice.fr.

Cell death & disease

|November 30, 2023

概括

针对第三组脑细胞母细胞瘤的代谢途径,特别是通过甘-3酸盐 (G3PS) 和马拉酸-酸盐 (MAS) 的NADH生产,为这种侵袭性的儿童大脑癌症提供了新的治疗策略.

科学领域:

儿科瘤学儿科瘤学
癌症新陈代谢癌症新陈代谢
神经瘤学神经瘤学

背景情况:

第三组髓母细胞瘤是一种具有很低生存率的侵袭性儿科脑瘤.
目前的治疗方法不足,原因是缺乏对第三组瘤细胞分子特征的理解.
在低氧环境中的代谢适应对3组瘤进展至关重要.

研究的目的:

在低毒的微环境中研究3组髓母细胞瘤细胞的代谢脆弱性.
通过探索NADH生产途径的作用来确定新的治疗点.
评估针对3组脑细胞母细胞瘤中的特定代谢酶和载体的有效性.

主要方法:

使用线粒体甘-3酸盐 (G3PS) 和酸盐-酸盐 (MAS) 穿机,分析NADH的产生.
用小分子向G3PS和MAS,Phenformin (线粒体复合体1抑制剂) 和乳酸脱酶A (LDHA) 抑制剂治疗3组细胞.
在不同度的氧气下评估细胞增殖,细胞亡和呼吸.
在3D人类小脑器官模型中进行验证.

主要成果:

第三组细胞利用G3PS和MAS进行NADH的产生.
针对G3PS和MAS的小分子显著降低了3组细胞的增殖和诱导细胞亡.
芬福明和LDHA抑制增强了细胞死亡,特别是在低氧条件下.
NADH穿抑制剂在3组人类大脑小器官中诱导了亡.

结论:

在脑髓母细胞瘤中存在代谢异质性,受氧水平的影响.
向NADH生产途径 (G3PS,MAS) 是对第三组髓母细胞瘤的一个有前途的治疗策略.
涉及代谢抑制剂的组合疗法可能会在侵袭性儿科脑瘤中克服治疗耐药性.

更多相关视频

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model

Published on: March 9, 2022

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

Published on: August 4, 2022

相关概念视频

Electron Transport Chain: Complex I and II

Electron Transport Chain: Complex I and II

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...

Mitochondrial Membranes

Mitochondrial Membranes

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,...

Translocation of Proteins into the Mitochondria

Translocation of Proteins into the Mitochondria

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,...