TMBIM-2通过促进Ca2+振荡来协调系统性线粒体应激反应
Jiasheng Li1,2, Jimeng Cui1,2, Xinyu Li1,2
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
The Journal of cell biology
|March 18, 2025
概括
神经元中的线粒体压力会触发信号,激活保护性反应. 这条由TMBIM-2调解的途径改善了学习,并延长了老化的虫的寿命.
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
- 衰老研究研究 衰老研究
背景情况:
- 神经元线粒体功能对生物体健康和组织间通信至关重要.
- 将神经元中的慢性线粒体压力与衰老和新陈代谢联系在一起的分子机制尚未完全理解.
研究的目的:
- 确定神经元线粒体展开蛋白反应 (UPRmt) 的关键介质.
- 阐明神经元线粒体应激在调节信号,神经传递和衰老中的作用.
主要方法:
- 使用Caenorhabditis elegans作为一个模型生物.
- 研究了神经元UPRmt.中XBX-6/TMBIM-2跨膜蛋白的功能.
- 分析了 (Ca2+) 振荡,血清素释放和学习行为.
主要成果:
- 确定XBX-6/TMBIM-2作为神经到肠道UPRmt的关键媒介.
- 证明神经元线粒体应激会通过MCA-3诱导TMBIM-2-依赖的Ca2+振荡.
- 表明持续的突触Ca2+振荡促进了血清素释放和UPRmt激活.
- 发现TMBIM-2水平随着年龄的增长而下降,其过度表达改善了厌恶性学习并延长了寿命.
结论:
- 慢性神经元线粒体压力通过TMBIM-2-依赖信号传输被整合到神经传输中.
- 这个过程驱动了代谢适应和行为修改,调节衰老.
- TMBIM-2 代表了与年龄相关的衰退的潜在治疗目标.
相关概念视频
01:45Mitochondrial Membranes
6.8K
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,...
6.8K
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
01:46Electron Transport Chain: Complex I and II
9.9K
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...
9.9K
01:19Translocation 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
01:37Energy to Drive Translocation
2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.0K
01:28The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K