Pharmacological targeting of the mitochondrial phosphatase PTPMT1 sensitizes hepatocellular carcinoma to ferroptosis

Protein tyrosine phosphatase mitochondrial 1 (PTPMT1), is a member of the protein tyrosine phosphatase superfamily localized on the mitochondrial inner membrane, and regulates the biosynthesis of cardiolipin. Given the important position of PTPMT1 in mitochondrial function and metabolism, pharmacological targeting of PTPMT1 is considered a promising manner in disease treatments. In this study, we mainly investigated the role of PTPMT1 in hepatocellular carcinoma (HCC) ferroptosis, a new type of cell death accompanied by significant iron accumulation and lipid peroxidation. Herein, the pharmacological inhibition of PTPMT1 was induced by alexidine dihydrochloride (AD, a dibiguanide compound). To elucidate the potential signaling associated with AD treatment, Hep 3B cells were administered AD (1 uM) for 24 hours, followed by harvesting for RNA-seq analysis.