LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, establishing the LKB1/AMPK/mTOR axis as a therapeutic target.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse |
| Journal | Chemico-Biological Interactions |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cbi.2026.112261 · PMID 42462870 |
In a TCE-sensitized mouse liver injury model, LKB1/AMPK deficiency aggravated mTOR-dependent impairment of mitophagy, causing mitochondrial DNA leakage and exacerbated immune-mediated liver damage. Rapamycin treatment, LKB1 overexpression, and AICAR (AMPK activator) each rescued mitophagy and reduced liver injury.
| Intervention | Rapamycin; AICAR; LKB1 overexpression |
| Target | LKB1/AMPK/mTOR axis; mitophagy |
| Model | Mouse |
| Effect | Rapamycin and AMPK activation restore mTOR-dependent mitophagy; LKB1/AMPK deficiency worsens mitochondrial DNA leakage and liver injury |