的特定酸化对线粒体功能和对压力因素的反应产生影响
Michael O Isei1, Peter A Girardi1, Joel Rodwell-Bullock1
1Department of Anesthesiology & Perioperative Medicine, University of Rochester, Rochester, New York, USA.
Journal of neurochemistry
|October 3, 2023
概括
化陶,阿尔茨海默病 (AD) 的标志,损害了线粒体功能. 上特定的酸化部位对线粒体分布,ATP水平产生负面影响,并增加对细胞压力因素的敏感性.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 阿尔茨海默病 (AD) 相关部位的陶蛋白酸化与疾病进展有关.
- 线粒体功能障碍的特征是酸化的增加,有助于AD的神经退行.
- fosforylation 在特定部位对线粒体功能的确切影响仍然不完全理解.
研究的目的:
- 调查AD相关的相仿性变异如何影响线粒体生物学.
- 阐明特定的酸化位影响线粒体功能和应激反应的机制.
主要方法:
- 工程化伪化结构 (2EC,2EM) 模仿AD相关化位.
- 陶变体在不朽化小鼠海马神经元细胞系中的表达.
- 评估线粒体分布,腺三酸盐 (ATP) 水平,反应性氧物种 (ROS) 生产和线粒体膜潜力.
主要成果:
- 相仿性改变了线粒体的分布,导致 soma 中的积累,并减少了神经元扩展.
- 在表达相仿变异的细胞中,ATP水平下降,ROS的产生增加.
- 线粒体膜潜力和ROS产量被特定的压力因素 (thapsigargin) 在具有相仿性tau的细胞中加剧.
结论:
- 在AD相关的表位上的酸化对线粒体功能产生不利影响.
- 线粒体功能障碍和应激反应的程度取决于tau上的特定酸化部位.
- 这些发现突出了酸化如何增强线粒体对压力因素的敏感性,从而导致AD等病变中的神经退行.
相关概念视频
Phosphorylation
50.5K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.5K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Protein Kinases and Phosphatases
13.2K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.2K
Microtubule Associated Proteins (MAPs)
4.4K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.4K
Translocation of Proteins into the Mitochondria
3.1K
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,...
3.1K


