MEN1/menin deficiency suppresses hepatocellular carcinogenesis via disrupting mitophagy-mediated mitochondrial homeostasis - PubMed
4 hours ago
- #MEN1
- #HCC
- #mitophagy
- MEN1/menin deficiency suppresses hepatocellular carcinoma (HCC) tumorigenesis in mice by disrupting mitochondrial homeostasis.
- MEN1 localizes to the outer mitochondrial membrane in HCC cells, mediated by its N-terminal sequence and the TOMM20 complex.
- Deficiency leads to impaired mitochondrial function: increased fission, reduced oxidative phosphorylation, lower ATP, and higher ROS.
- MEN1 loss inhibits mitophagy via downregulation of the PINK1-PRKN pathway, causing accumulation of dysfunctional mitochondria.
- In human HCC, high MEN1 expression correlates with poor clinical outcomes and is linked to autophagy signatures.
- Pharmacological activation of mitophagy reverses the tumor-suppressive effects of MEN1 deficiency in experimental models.