相关实验视频
Updated: May 5, 2026

08:35
Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
7.4K
Bcl-x(L) 将Bax从线粒体逆转移到细胞质中
Frank Edlich1, Soojay Banerjee, Motoshi Suzuki
1Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|April 5, 2011
概括
幸存者Bcl-2蛋白,像Bcl-x(L一样,通过不断将Bax从线粒体返回细胞质中来抑制细胞灭绝. 这种逆转移机制使巴克斯保持其不活跃的细胞质状态.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 巴克斯蛋白通过转移到线粒体和透外膜来启动亡.
- 幸存者Bcl-2蛋白质抵消了Bax,但由于缺乏稳定的复合物或局部化,它们的抑制机制尚不清楚.
- 了解巴克斯调节对于控制被编程细胞死亡至关重要.
研究的目的:
- 调查Bcl-2蛋白质抑制Bax介导的亡的生存机制.
- 要确定巴克斯从线粒体的逆转移是否是一个关键的调节步骤.
- 阐明Bcl-x(L) 在维持细胞质中Bax的作用.
主要方法:
- 利用分子内二硫化连接物来约束Bax在细胞内的原生细胞溶液构成中.
- 使用光漂白中的光损失 (FLIP) 来追踪Bax转位动态.
- 评估了线粒体外膜透活性 (MOMP) 在体外和细胞内.
主要成果:
- 巴克斯干扰了Bcl-x(L) 相互作用和无细胞MOMP活动,但导致巴克斯在线粒体上积聚.
- 在健康细胞中,FLIP证明了野生型巴克斯从线粒体到细胞质的持续逆转移.
- 绑定的巴克斯显示显著减少了逆转移,与线粒体积累相关.
- 巴克斯逆转移取决于生存的Bcl-2家族蛋白质.
结论:
- 幸存者Bcl-2蛋白质,特别是Bcl-x(L,通过促进其从线粒体回到细胞质中持续的逆转移来抑制Bax.
- 这种连续的逆转移是维持巴克斯在不活跃的细胞质状态并防止亡的主要机制.
- 准巴克斯逆转移可能为涉及异常亡的疾病提供新的治疗策略.
相关概念视频
Intralumenal Vesicles and Multivesicular Bodies
4.0K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
4.0K
Translocation of Proteins into the Mitochondria
8.8K
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,...
8.8K
Protein Transport into the Inner Mitochondrial Membrane
3.5K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.5K
Post-translational Translocation of Proteins to the RER
5.6K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
5.6K
Export of Misfolded Proteins out of the ER
4.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.3K
The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K

