Department of Biochemistry, University of Lausanne, Chemin Des Boveresses 155, 1066 Epalinges, Switzerland.
Joint Bone Spine. 2018 Jul;85(4):423-428. doi: 10.1016/j.jbspin.2017.06.005. Epub 2017 Jul 10.
Key cellular functions including those related to energy metabolism, organization of the genetic information or production of membrane-bound and secreted proteins are compartmentalized within organelles. Various stresses such as differentiation programs, viral and bacterial infections, perturbations in protein production, mechanical constraints, changes in the environment and nutriment accessibility can impact cellular homeostasis and organelle integrity. Perturbations of these cellular compartments trigger repair and adaptation programs aimed at restoring homeostasis. These events are often associated with low-grade inflammation also termed parainflammation. While the nature and mechanisms of danger signals released by irremediably damaged cells are well understood, how transiently stressed cells trigger inflammation is still poorly understood. Emerging studies highlighted new mechanisms by which stress pathways promote inflammation. Cytosolic innate immune pathways are engaged by signals stemming from perturbed organelles such as the mitochondria, the endoplasmic reticulum (ER) or the nuclear envelope (NE). These observations indicate that these pathways function as guardians of cellular homeostasis and may contribute to disease in pathologies characterized by perturbations of cellular homoeostasis. Mitochondria-stress, ER-stress or NE-stress are emerging as proinflammatory signals that contribute to human conditions and diseases.
关键细胞功能，包括与能量代谢、遗传信息组织或膜结合和分泌蛋白的产生有关的功能，都在细胞器内进行分区。各种应激，如分化程序、病毒和细菌感染、蛋白质生产的干扰、机械约束、环境变化和营养物质可及性，都可能影响细胞内稳态和细胞器的完整性。这些细胞区室的扰动会触发修复和适应程序，旨在恢复内稳态。这些事件通常与低水平炎症（也称为类炎症）有关。虽然不可逆损伤细胞释放的危险信号的性质和机制已被充分了解，但暂时受到应激的细胞如何引发炎症仍知之甚少。新的研究强调了应激途径促进炎症的新机制。细胞质先天免疫途径被来自受扰细胞器（如线粒体、内质网（ER）或核膜（NE））的信号激活。这些观察结果表明，这些途径作为细胞内稳态的守护者发挥作用，并可能在以细胞内稳态紊乱为特征的病理中导致疾病。线粒体应激、内质网应激或核膜应激作为促炎信号，与人类疾病有关。
