Technische Universität München, Chair for Biofunctionality, ZIEL, Research Center for Nutrition and Food Science, CDD, Center for Diet and Disease, Freising-Weihenstephan, Germany.
Inflamm Bowel Dis. 2012 Jul;18(7):1364-77. doi: 10.1002/ibd.21944. Epub 2011 Dec 19.
Inflammatory bowel diseases (IBDs), like many other chronic diseases, feature multiple cellular stress responses including endoplasmic reticulum (ER) unfolded protein response (UPR). Maintaining protein homeostasis is indispensable for cell survival and, consequently, distinct signaling pathways have evolved to transmit organelle stress. While the ER UPR, aiming to restore ER homeostasis after challenges to ER function, has been extensively studied in the context of chronic diseases, only recently the related mitochondrial UPR (mtUPR), induced by disturbances of mitochondrial proteostasis, has drawn some attention. ER and mitochondria are in close contact and interact physically and functionally. Accumulating data have placed mitochondria at the center of diverse cellular functions and suggest mitochondria as integrators of signaling pathways such as autophagy and inflammation. Consequently, it is likely that mitochondrial stress and ER stress cannot be regarded separately and that mitochondrial stress, as well as ER stress, participates in the pathology of IBD. Protein homeostasis is particularly sensitive toward infections, oxidative stress, and energy deficiency. Thus, environmental disturbances impacting organelle function lead to the concerted activation of distinct UPRs. The metabolic status might therefore serve as an innate mechanism to sense the epithelial environment, including luminal-derived and host-derived factors. This review highlights mtUPR and its interrelation with ER UPR, focuses on recent studies identifying mitochondria as integrators of cellular danger signaling, and, furthermore, illustrates the importance ER UPR and mitochondrial dysfunction in IBD.
炎症性肠病 (IBD) 与许多其他慢性疾病一样，具有多种细胞应激反应，包括内质网 (ER) 未折叠蛋白反应 (UPR)。维持蛋白质的内稳态对于细胞的存活是必不可少的，因此，已经进化出不同的信号通路来传递细胞器的应激。虽然 ER UPR 的目的是在 ER 功能受到挑战后恢复 ER 的内稳态，但在慢性疾病的背景下，已经进行了广泛的研究，而最近才引起人们对与线粒体蛋白质稳态紊乱相关的线粒体 UPR (mtUPR) 的关注。ER 和线粒体密切接触，在物理和功能上相互作用。越来越多的证据表明，线粒体处于多种细胞功能的中心，并暗示线粒体作为自噬和炎症等信号通路的整合者。因此，很可能不能将线粒体应激和 ER 应激分开，并且线粒体应激以及 ER 应激参与 IBD 的病理学。蛋白质的内稳态对感染、氧化应激和能量缺乏特别敏感。因此，影响细胞器功能的环境干扰会导致不同的 UPR 协同激活。因此，代谢状态可能是一种先天的机制，用于感知上皮环境，包括腔衍生和宿主衍生的因素。这篇综述强调了 mtUPR 及其与 ER UPR 的相互关系，重点介绍了最近的研究，这些研究将线粒体确定为细胞危险信号的整合者，并进一步说明了 ER UPR 和线粒体功能障碍在 IBD 中的重要性。
