AMPK激活在几分钟内降低了TXNIP,Rab5和Rab7的调节,从而抑制了人类致病病毒的内细胞质介导的进入
Viktoria Diesendorf1, Veronica La Rocca1,2, Michelle Teutsch1
1Institute of Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, 97078 Würzburg, Germany.
Cells
|March 12, 2025
概括
AMP激活蛋白激酶 (AMPK) 和ULK1激活抑制细胞内细胞结核,通过向该过程的后期阶段来阻止SARS-CoV-2等多种RNA病毒的进入.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 代谢过程中的代谢.
背景情况:
- 细胞代谢动态地适应环境变化,包括营养的可用性.
- 低血糖条件激活AMP激活蛋白激酶 (AMPK) 途径.
研究的目的:
- 研究AMPK和ULK1在调节内细胞和病毒进入中的作用.
- 确定AMPK/ULK1激活对各种RNA病毒的影响.
主要方法:
- 使用药理剂激活AMPK和ULK1通路.
- 在细胞培养物,肺切片和有机体中评估德克斯的吸收和病毒进入 (包裹和非包裹RNA病毒).
- 对内细胞因子 (TXNIP,Rab5,Rab7,LAMP1,GRP78) 和病毒RNA/蛋白质水平的分析.
- 抑制PI3K和mTORC2通路的作用.
主要成果:
- AMPK/ULK1激活显著抑制了包括SARS-CoV-2在内的各种RNA病毒的受体介导内细胞分裂.
- 在受体结合后的阶段,通过不同的途径阻止病毒的进入.
- AMPK激活通过转化抑制降低了TXNIP,并通过转化失活和蛋白质酶体降解降低了Rab5/Rab7.
- AMPK激活损害了SARS-CoV-2的晚期复制,并减少了内溶酶体标志物.
- 抑制PI3K/mTORC2通路增强了AMPK活性,并阻止了病毒的进入.
结论:
- AMPK和ULK1作为细胞限制因子对抗内细胞分裂.
- 激活AMPK/ULK1阻碍了包裹和非包裹RNA病毒的进入.
- 针对AMPK通路提供了一个潜在的策略来抑制病毒感染.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
Receptor-mediated Endocytosis
5.9K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
5.9K
Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
Recycling Endosomes and Transcytosis
2.6K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.6K
Rab Cascades
2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K


