Misawa Takuma, Takahama Michihiro, Saitoh Tatsuya
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA.
Division of Inflammation Biology, Institute for Enzyme Research, Tokushima University, Tokushima, 770-8503, Japan.
Adv Exp Med Biol. 2017;997:187-197. doi: 10.1007/978-981-10-4567-7_14.
Mitochondria and the endoplasmic reticulum (ER) are fundamental organelles that coordinate high-order cell functions. Mitochondria are centers of energy production, whereas the ER is responsible for folding, transport, and degradation of proteins. In addition to their specific functions, mitochondria and ER actively communicate with each other to promote a variety of cellular events, such as material transfer and signal transduction. Recent studies have shown the critical involvement of these organelles in regulation of the innate immune system, which functions in host defense. The innate immune system utilizes a wide range of germ-line-encoded pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and induces inflammatory and antiviral responses. Contact sites between mitochondria and the ER function in assembly of the NLR family pyrin domain containing 3 (NLRP3)-inflammasome to promote the inflammatory response. The NLRP3-inflammasome is a protein complex composed of the receptor NLRP3 on the ER side and the adaptor apoptosis-associated speck-like protein containing a CARD on the mitochondrial side; it induces caspase-1-dependent maturation of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Furthermore, ER-mitochondria contact sites function in initiation and mediation of signal transduction pathways downstream of intracellular PRRs, such as retinoic acid-inducible gene I-like receptor and cyclic GMP-AMP synthase, to promote the antiviral response. Therefore, ER-mitochondria contact sites, also known as mitochondria-associated membranes, play key roles in regulation of innate immune responses.
线粒体和内质网（ER）是协调高阶细胞功能的基本细胞器。线粒体是能量产生的中心，而内质网负责蛋白质的折叠、运输和降解。除了它们的特定功能外，线粒体和内质网还积极相互沟通，以促进各种细胞活动，如物质转运和信号转导。最近的研究表明，这些细胞器在宿主防御中起作用的固有免疫系统的调节中起着关键作用。固有免疫系统利用多种种系编码的模式识别受体（PRR）来识别病原体相关分子模式（PAMP）和损伤相关分子模式（DAMP），并诱导炎症和抗病毒反应。线粒体和内质网之间的接触位点在含NLR家族pyrin结构域3（NLRP3）炎性小体的组装中发挥作用，以促进炎症反应。NLRP3炎性小体是一种蛋白质复合物，由内质网一侧的受体NLRP3和线粒体一侧的含有CARD的衔接蛋白凋亡相关斑点样蛋白组成；它诱导半胱天冬酶-1依赖性促炎细胞因子如白细胞介素（IL）-1β和IL-18的成熟。此外，内质网-线粒体接触位点在细胞内PRR下游的信号转导途径的启动和介导中发挥作用，如视黄酸诱导基因I样受体和环鸟苷酸-腺苷酸合酶，以促进抗病毒反应。因此，内质网-线粒体接触位点，也称为线粒体相关膜，在固有免疫反应的调节中起关键作用。
