Helicobacter hepaticus promotes hepatic steatosis through CdtB-induced mitochondrial stress and lipid metabolism reprogramming.

ABSTRACT: Host-pathogen interaction influences many non-infectious diseases, including metabolic diseases. Helicobacter hepaticus (H. hepaticus) has been found in some metabolic dysfunction-associated steatotic liver disease (MASLD) patients, however, the causal link and underlying mechanisms remain unclear. Here we report that H. hepaticus infection or overexpression of CdtB of H. hepaticus induces lipid deposition in hepatocytes, both in vivo and in vitro. Furthermore, we identify that CdtB translocates to mitochondria with the help of Hsp90, interacts with ATP5A1, reduces mitochondrial respiratory complex V activity, damages mitochondria, and disrupts lipid metabolism. Mechanistically, CdtB-induced lipogenesis depends on the CdtB-mitochondrial ROS-mTORC1-SREBP1 axis and CdtB-mediated NONO express

SUBMITTER: Jin S 

PROVIDER: S-EPMC12381262 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature