promotes gastric cancer through CagA-mediated mitochondrial cholesterol accumulation by targeting CYP11A1 redistribution.

Cholesterol and () are both risk factors for gastric cancer (GC). However, the relationship between cholesterol and and their function in the progression of GC are controversial. In this study, we addressed that 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 -induced cholesterol accumulation. and 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 infection inhibited mitophagy and maintained the mitochondria homeostasis. could contribute to the progression of GC through the CagA/CYP11A1-mitoCHO axis. This study demonstrates that can contribute to the progression of GC via cholesterol, and eradicating is still prognostically beneficial to GC patients.