Hsp90 C-terminal domain inhibition enhances ferroptosis by disrupting GPX4-VDAC1 interaction to increase HMOX1 release from oligomerized VDAC1 channels.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Given the critical role of liver in iron storage and metabolism, ferroptosis, characterized by iron-dependent lipid peroxidation and oxidative damage, has become a potential therapy for HCC. Recent research indicated that Voltage-dependent anion-selective channel protein 1 (VDAC1), a key gatekeeper on the outer mitochondrial membrane (OMM), promotes ferroptosis in its oligomeric form. While oxidative stress is known to promote VDAC1 oligomerization, the relationship between oxidative modifications such as carbonylation and VDAC1 oligomerization remains poorly understood. Additionally, it is uncertain whether oligomerized VDAC1 channels facilitate the release of ferroptosis-related molecules. Our res

SUBMITTER: Li J 

PROVIDER: S-EPMC12172306 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature