线粒体腺酶通过调节氧酸盐和线粒体未折叠蛋白质反应来抑制免疫力
Eunah Kim1, Andrea Annibal2, Yujin Lee1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
Nature communications
|June 22, 2023
概括
线粒体氨基酸酶 (ACO-2) 抑制免疫力. 抑制ACO-2可促进线粒体未折叠蛋白质反应,增强C. elegans和人类细胞中的细菌感染防御能力.
科学领域:
- 免疫学 免疫学 免疫学
- 线粒体生物学 线粒体生物学
- 代谢途径 代谢途径
背景情况:
- 人们越来越认识到线粒体在免疫反应中的关键作用.
- 线粒体克雷布斯循环对免疫的具体贡献,特别是在生物体水平上,尚不清楚.
研究的目的:
- 研究 mitochondrial aconitase (ACO-2),一个克雷布斯循环酶,在对细菌病原体的免疫力中的作用.
- 阐明ACO-2在体内和体外影响免疫反应的分子机制.
主要方法:
- 在模型生物C. elegans. 中对aco-2基因的遗传抑制.
- 测量氧化酸盐水平和线粒体未折叠蛋白反应 (UPRmt).
- 对转录因子ATFS-1在免疫中的作用的分析.
- 在培养的哺乳动物细胞中进行实验验证,使用基因抑制ACO2.
主要成果:
- 在C. elegans中,aco-2的遗传抑制导致了氧化酸盐水平的降低.
- 这种减少触发了线粒体展开蛋白反应 (UPRmt) 的增加.
- 转录因子ATFS-1的升级导致对病原性细菌的免疫力增强.
结论:
- 线粒体氨基酸酶 (ACO-2) 作为抗细菌感染免疫力的抑制剂.
- 该机制涉及减少氧酸盐水平,激活UPRmt,以及随后的ATFS-1-介导的免疫增强.
- 向ACO2代表了一种潜在的治疗策略,用于调节人类的免疫力,因为它的保护性质.
相关概念视频
Electron Transport Chain: Complex I and II
14.6K
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...
14.6K
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 Membranes
11.6K
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,...
11.6K
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
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
Mitochondria
13.9K
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,...
13.9K


