胆固醇和幽门螺杆菌（H. pylori）都是胃癌（GC）的危险因素。然而，胆固醇和幽门螺杆菌之间的关系以及它们在GC进展中的作用仍存在争议。在这项研究中，我们发现幽门螺杆菌可以诱导线粒体胆固醇积累，促进GC增殖，并通过胆固醇保护GC细胞免于凋亡。使用代谢组学和转录组学测序来鉴定负责幽门螺杆菌诱导的胆固醇积累的 CYP11A1。体外和体内功能实验表明，胆固醇可以促进GC增殖并抑制细胞凋亡。从机械角度来看，细胞毒素相关基因 A (CagA) 和 CYP11A1 的相互作用使线粒体 CYP11A1 在线粒体外重新分布，随后导致线粒体胆固醇积累。 CYP11A1 敲低可上调胆固醇积累，并以胆固醇依赖性方式重现胆固醇对 GC 的影响。此外，CYP11A1 敲低或幽门螺杆菌感染抑制线粒体自噬并维持线粒体稳态。幽门螺杆菌可能通过 CagA/CYP11A1-mitoCHO 轴促进 GC 的进展。这项研究表明，幽门螺杆菌可以通过胆固醇促进胃癌的进展，根除幽门螺杆菌仍然对胃癌患者的预后有益。© 作者。

Cholesterol and Helicobacter pylori (H. pylori) are both risk factors for gastric cancer (GC). However, the relationship between cholesterol and H. pylori and their function in the progression of GC are controversial. In this study, we addressed that H. pylori could induce mitochondrial cholesterol accumulation and promote GC proliferation and protect GC cells against apoptosis via cholesterol. Metabolomic and transcriptomic sequencing were used to identify CYP11A1 responsible for H. pylori-induced cholesterol accumulation. In vitro and in vivo function experiments revealed that cholesterol could promote the proliferation of GC and inhibit apoptosis. Mechanically, the interaction of Cytotoxin-associated gene A (CagA) and CYP11A1 redistributed mitochondrial CYP11A1 outside the mitochondria and subsequently caused mitochondrial cholesterol accumulation. The CYP11A1-knockdown upregulated cholesterol accumulation and reproduced the effect of cholesterol on GC in a cholesterol-dependent manner. Moreover, CYP11A1-knockdown or H. pylori infection inhibited mitophagy and maintained the mitochondria homeostasis. H. pylori could contribute to the progression of GC through the CagA/CYP11A1-mitoCHO axis. This study demonstrates that H. pylori can contribute to the progression of GC via cholesterol, and eradicating H. pylori is still prognostically beneficial to GC patients.© The author(s).