biostudies-literatureUnknown15(12)Shao LPancreatic β-cell apoptosis plays a crucial role in the development of type 2 diabetes. Cytochrome c oxidase subunit 6A2 (COX6A2) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells, however, whether they are involved in β-cell apoptosis is unclear. Here, we sought to investigate the role of FXR-regulated COX6A2 in diabetic β-cell apoptosis. We found that COX6A2 expression was increased in islets from diabetic animals, whereas FXR expression was suppressed. Notably, overexpression of COX6A2 facilitated β-cell apoptosis, whereas its deficiency attenuated this process and ameliorates type 2 diabetes, suggesting a pro-apoptotic role of COX6A2 in β-cells. Mechanistically, increased COX6A2 interacted with and enhanced the expression of voltage-dependent anion channel 1 (VDCell death & disease920https://www.ebi.ac.uk/biostudies/studies/S-EPMC11659401biostudies-literatureFXR-regulated COX6A2 triggers mitochondrial apoptosis of pancreatic β-cell in type 2 diabetes.PMC11659401Shao LMa XYing YLv SYan DShu XKong XAi XfalseFXR-regulated COX6A2 triggers mitochondrial apoptosis of pancreatic β-cell in type 2 diabetes.Pancreatic β-cell apoptosis plays a crucial role in the development of type 2 diabetes. Cytochrome c oxidase subunit 6A2 (COX6A2) and Farnesoid X Receptor (FXR) have been identified in pancreatic β-cells, however, whether they are involved in β-cell apoptosis is unclear. Here, we sought to investigate the role of FXR-regulated COX6A2 in diabetic β-cell apoptosis. We found that COX6A2 expression was increased in islets from diabetic animals, whereas FXR expression was suppressed. Notably, overexpression of COX6A2 facilitated β-cell apoptosis, whereas its deficiency attenuated this process and ameliorates type 2 diabetes, suggesting a pro-apoptotic role of COX6A2 in β-cells. Mechanistically, increased COX6A2 interacted with and enhanced the expression of voltage-dependent anion channel 1 (VD2024-01-01T00:00:00Z2024 Dec2025-04-26T17:10:37.945Z2025-04-06T15:25:10.764ZS-EPMC116594013970252710.1038/s41419-024-07302-4