相关实验视频
Updated: Jul 25, 2025

09:01
Measurement of Protein Import Capacity of Skeletal Muscle Mitochondria
Published on: January 7, 2022
2.7K
细胞内膜网的未折叠蛋白质反应通过缓冲非进口蛋白质来支持线粒体生物发生
Katharina Knöringer1, Carina Groh1, Lena Krämer1
1Cell Biology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Molecular biology of the cell
|June 28, 2023
概括
线粒体蛋白质被误导到内质网膜 (ER) 引发了未折叠的蛋白质反应 (UPR). 当线粒体进口受损或蛋白质需求增加时,这种ER通路保持细胞平衡.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 蛋白质平衡是蛋白质的平衡.
背景情况:
- 大多数线粒体蛋白质在细胞质中合成,并进口到线粒体中.
- 线粒体功能障碍可能导致前体蛋白质的积累,挑战细胞蛋白质平衡.
- 细胞内膜网膜 (ER) 在蛋白质折叠和质量控制中起着至关重要的作用.
研究的目的:
- 为了研究细胞对被阻断的线粒体蛋白质的反应.
- 在各种条件下确定线粒体前体蛋白的局部和命运.
- 为了阐明表达蛋白质响应在内分泌网膜 (UPRER) 中对线粒体应激反应的作用.
主要方法:
- 阻止蛋白质转移到线粒体.
- 使用细胞成像技术分析线粒体膜蛋白的局部化.
- 监测内质网膜内未折叠的蛋白质反应的激活.
主要成果:
- 阻断线粒体进口会导致线粒体膜蛋白在ER中积聚.
- 这种积累触发了UPRER,表明了ER压力.
- 在正常生理条件下,线粒体膜蛋白也在ER中存在.
- 居住在ER的线粒体前体随着进口缺陷和代谢刺激而增加.
- 在这些条件下,UPRER对于维持蛋白质平衡和细胞健康至关重要.
结论:
- 对于不能立即进口的线粒体前体蛋白质来说,ER充当了缓冲区.
- 当线粒体前体水平上升时,UPRER被激活以管理ER的蛋白质折叠能力.
- 这种机制在线粒体压力或增加蛋白质合成期间对细胞健康至关重要.
相关概念视频
The Unfolded Protein Response
4.8K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.8K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Translocation of Proteins into the Mitochondria
3.2K
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,...
3.2K
Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
Mitochondrial Precursor Proteins
2.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.6K
Export of Misfolded Proteins out of the ER
3.7K
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...
3.7K

