铜神经毒性的线粒体通路:专注于线粒体动力学和线粒体
Michael Aschner1, Anatoly V Skalny2,3,4, Rongzhu Lu5
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States.
Frontiers in molecular neuroscience
|December 20, 2024
概括
过多的铜会破坏脑细胞,破坏线粒体,改变它们的形状,损害清洁过程. 这种神经毒性可能可以通过向线粒体健康的药物来预防.
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
- 毒理学 毒理学 毒理学
背景情况:
- 铜 (Cu) 对大脑功能至关重要,但过量有毒,与神经退行有关.
- 神经毒性涉及线粒体功能障碍,但其对线粒体动力学和线粒体的影响仍有争议.
研究的目的:
- 审查线粒体功能障碍在铜诱导的神经毒性的作用.
- 重点是脑细胞中线粒体融合,裂变和线粒体细胞分裂的变化.
主要方法:
- 现有文献的叙述性审查.
- 对铜对线粒体动力学 (融合/裂变) 和线粒体衰变的影响研究的分析.
- 对所涉及的分子通路的检查 (Opa1,Mfn1/2,Drp1,PINK1/Parkin,PGC-1α).
主要成果:
- 铜抑制线粒体融合,通过改变关键蛋白质表达来促进裂变.
- 铜会触发PINK1/帕金-依赖性线粒,这是一个补偿反应.
- 慢性高剂量的铜会损害线粒体和线粒体生物发生,恶化功能障碍.
- 铜通过蛋白质毒性压力诱导cuproptosis,导致大脑疾病.
结论:
- 线粒体动力学和线粒体细胞失调是铜诱导的神经毒性的关键.
- 线粒体质量控制受损会加剧铜对大脑的破坏性影响.
- 针对线粒体质量控制的线粒体保护策略可以防止铜神经毒性.
相关概念视频
Electron Transport Chain: Complex I and II
11.3K
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...
11.3K
Mitochondrial Membranes
8.3K
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,...
8.3K
Translocation of Proteins into the Mitochondria
3.0K
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,...
3.0K
Mitochondria
10.7K
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,...
10.7K
Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K


