由线粒体核酸激活先天免疫的机制和作用
Prashant Rai1, Michael B Fessler1
1Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
International immunology
|August 30, 2024
概括
线粒体释放DNA和RNA来放大先天免疫信号,并提醒细胞应对压力. 这一过程涉及线粒体核酸转位,在宿主防御和自身免疫性疾病中起作用.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体越来越多地被认为是它们在天生的免疫力中的关键作用.
- 线粒体核酸 (DNA和RNA) 可以从线粒体矩阵转移到细胞质和内分泌体.
- 这种转位作为先天免疫反应中的信号事件.
研究的目的:
- 审查线粒体核酸错位化的分子机制.
- 讨论这些机制在宿主防御,自身免疫和自身炎症性疾病中的作用.
- 突出主体衍生DNA的范式,作为免疫信号放大器和器官恒温的警报.
主要方法:
- 审查关于线粒体核酸转位的现有文献.
- 讨论涉及线粒体膜重塑和囊泡运输的分子途径.
- 对细胞和内溶体核酸传感器 (例如cGAS,RIG-I,TLR7,TLR9) 的激活的分析.
主要成果:
- 线粒体DNA和RNA通过调节的机制进入细胞体和内分泌体.
- 激活的核酸受体诱导I型干扰素和促炎细胞因子.
- 主体衍生的线粒体DNA放大了先天的免疫反应,并发出了器官应激信号.
结论:
- 线粒体核酸转位是先天免疫和宿主防御的关键机制.
- 这些通路的失调有助于自身免疫和自身炎症性疾病.
- 了解这些机制可能会导致人类疾病的新型治疗干预措施.
相关概念视频
Animal Mitochondrial Genetics
7.5K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.5K
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
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
Mitochondria
11.5K
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,...
11.5K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
Cytotoxic T Cells-mediated Immune Response
861
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
861


