澄胺结合蛋白NIPSNAP1和2通过线粒体质量控制来调节细胞因子的产生
Soh Yamamoto1, Noriko Ogasawara2,3, Yukari Mitsuhashi1
1Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Scientific reports
|January 29, 2024
概括
克拉里思素 (CAM) 通过暂时抑制NIPSNAP蛋白来抑制炎症,影响线粒体功能,并通过TLR-线粒体轴减少IL-8的产生.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 麦克罗利德抗生素 (如克拉利胺素 (CAM)) 的抗炎机制尚未完全理解.
- NIPSNAP 1 和 2 蛋白质与免疫反应和线粒体健康有关.
- 在CAM,NIPSNAP蛋白,线粒体和托尔类受体 (TLRs) 之间的相互作用是不清楚的.
研究的目的:
- 研究由NIPSNAP1/2调节的线粒体平衡与CAM的免疫调节作用之间的关系.
- 为了阐明CAM-NIPSNAP-线粒体-TLR轴在炎症中的分子机制.
主要方法:
- 对于NIPSNAP1/2敲击 (KD) 的RNA干扰 (RNAi).
- 通过柔性分析仪使用氧气消耗率 (OCR) 评估线粒体功能.
- 在NIPSNAP的淘汰和淘汰细胞中,对托尔类受体4 (TLR4) 中介的互白素-8 (IL-8) 生产的分析.
主要成果:
- NIPSNAP1/2 KD或线粒体抑制剂治疗损害了TLR4介导的IL-8产生.
- 在NIPSNAP1/2淘汰细胞中,IL-8分泌没有受到影响.
- 线粒体OCR在NIPSNAP1/2KD细胞中降低,但在淘汰细胞中没有降低;CAM也因剂量而降低了OCR.
结论:
- 通过线粒体质量控制,CAM抑制IL-8的产生,包括暂时抑制NIPSNAP1/2.2.
- 研究结果揭示了一种新的TLR-线粒体轴和类免疫调节通路.
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
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
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
The Nucleolus
8.8K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.8K
Mitochondrial Protein Sorting
4.3K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.3K
Riboswitches
8.1K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.1K


