Department of Infection Biology, Chungnam National University School of Medicine, Daejeon 35015, Korea.
Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.
Int J Mol Sci. 2020 Jul 1;21(13):4714. doi: 10.3390/ijms21134714.
The inflammasome is a large intracellular protein complex that activates inflammatory caspase-1 and induces the maturation of interleukin (IL)-1β and IL-18. Mitophagy plays an essential role in the maintenance of mitochondrial homeostasis during stress. Previous studies have indicated compelling evidence of the crosstalk between inflammasome and mitophagy. Mitophagy regulation of the inflammasome, or vice versa, is crucial for various biological functions, such as controlling inflammation and metabolism, immune and anti-tumor responses, and pyroptotic cell death. Uncontrolled regulation of the inflammasome often results in pathological inflammation and pyroptosis, and causes a variety of human diseases, including metabolic and inflammatory diseases, infection, and cancer. Here, we discuss how improved understanding of the interactions between inflammasome and mitophagy can lead to novel therapies against various disease pathologies, and how the inflammasome-mitophagy connection is currently being targeted pharmacologically by diverse agents and small molecules. A deeper understanding of the inflammasome-mitophagy connection will provide new insights into human health and disease through the balance between mitochondrial clearance and pathology.
炎症小体是一种大型细胞内蛋白复合物,可激活炎症性胱天蛋白酶-1,并诱导白细胞介素 (IL)-1β 和 IL-18 的成熟。线粒体自噬在应激过程中维持线粒体动态平衡方面发挥着重要作用。先前的研究表明炎症小体和线粒体自噬之间存在着强烈的相互作用。线粒体自噬对炎症小体的调节,或反之,对各种生物学功能至关重要,如控制炎症和代谢、免疫和抗肿瘤反应以及细胞焦亡。炎症小体的调控失控通常会导致病理性炎症和细胞焦亡,并导致多种人类疾病,包括代谢和炎症性疾病、感染和癌症。在这里,我们讨论了对炎症小体和线粒体自噬之间相互作用的理解如何能够导致针对各种疾病病理的新疗法,以及炎症小体-线粒体自噬连接目前如何通过不同的药物和小分子被药理学靶向。对炎症小体-线粒体自噬连接的更深入了解将通过线粒体清除和病理学之间的平衡为人类健康和疾病提供新的见解。