Key Laboratory of Endemic and Ethnic Minority Diseases, Ministry of Education & Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang, 550004, China.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Sci Rep. 2024 Sep 17;14(1):21648. doi: 10.1038/s41598-024-72534-5.
Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.
幽门螺杆菌（H. pylori）是世界上最常见的细菌感染之一，其关键毒力成分 CagA 是导致胃癌的主要原因。自噬是一种选择性自噬形式，可消除受损的线粒体，对于某些病毒和细菌逃避免疫系统至关重要。然而，CagA 介导 H. pylori 诱导的线粒体自噬和 NLRP3 炎性体激活的机制仍不清楚。在这项研究中，我们报道 H. pylori 主要利用其 CagA 诱导线粒体氧化损伤、线粒体功能障碍、动态失衡，并阻断自噬流。抑制线粒体自噬会导致 NLRP3 炎性体激活和细胞凋亡增加，以及 H. pylori 感染细胞活力降低。我们的研究结果表明，H. pylori 通过 CagA 诱导线粒体功能障碍和线粒体自噬。它降低 NLRP3 炎性体激活以逃避宿主免疫监视，并增加感染细胞的存活和活力，可能导致胃癌的发生和发展。我们的研究结果为 H. pylori 诱导的胃癌发病机制提供了新的见解，抑制线粒体自噬可能是预防和治疗这种疾病的新方法之一。
