biostudies-literatureUnknown56(12)Ko MMetformin (MetF) is used worldwide as a first-line therapy for type 2 diabetes. Recently, interest in the pleiotropic effects of MetF, such as its anticancer and antiaging properties, has increased. However, the molecular target of MetF and the detailed mechanism underlying its ability to inhibit cell growth through autophagy induction remain incompletely understood. In this study, using an innovative label-free drug affinity responsive target stability (DARTS)-LC-MS/MS method, we discovered that mitochondrial voltage-dependent anion channel 1 (VDAC1) is a novel binding protein involved in the induction of autophagy-related cell death by high-dose MetF in hepatocellular carcinoma (HCC). Computational alanine scanning mutagenesis revealed that MetF and VDAC1 (D9, E203) interact electrostatiExperimental & molecular medicine2714-2725https://www.ebi.ac.uk/biostudies/studies/S-EPMC11671597biostudies-literatureThe anticancer effect of metformin targets VDAC1 via ER-mitochondria interactions-mediated autophagy in HCC.PMC11671597Choi SKo MLazim RKim JYKwon HJGosu VKim JLee YLee JYfalseThe anticancer effect of metformin targets VDAC1 via ER-mitochondria interactions-mediated autophagy in HCC.Metformin (MetF) is used worldwide as a first-line therapy for type 2 diabetes. Recently, interest in the pleiotropic effects of MetF, such as its anticancer and antiaging properties, has increased. However, the molecular target of MetF and the detailed mechanism underlying its ability to inhibit cell growth through autophagy induction remain incompletely understood. In this study, using an innovative label-free drug affinity responsive target stability (DARTS)-LC-MS/MS method, we discovered that mitochondrial voltage-dependent anion channel 1 (VDAC1) is a novel binding protein involved in the induction of autophagy-related cell death by high-dose MetF in hepatocellular carcinoma (HCC). Computational alanine scanning mutagenesis revealed that MetF and VDAC1 (D9, E203) interact electrostati2024-01-01T00:00:00Z2024 Dec2026-05-02T14:27:45.069Z2025-04-04T02:36:38.231ZS-EPMC116715973962745110.1038/s12276-024-01357-1