Investigating the role of mitoNEET in iron overload-induced insulin resistance

Excess iron, in a process termed iron overload (IO) is closely linked to cardiovascular and metabolic diseases. Previous research has already established a causal link between IO and insulin resistance in both cardiac and skeletal muscle setting. Building upon this knowledge, the potential for mitoNEET to offer protection against IO-induced insulin resistance was investigated. The potential mechanisms underlying the protective effects of mitoNEET, which included mitochondrial dynamics, oxidative stress, and mitophagy, was also examined in H9c2 cardiac and L6 skeletal muscle cells. Using various experimental approaches including quantitative polymerase chain reaction (qPCR), western blot, fluorescent microscopy, and reporter cell lines, mitoNEET was shown to be protective against IO-induced insulin resistance. In H9c2 cells, mitoNEET provided protection by regulating mitochondrial iron and reactive oxygen species (ROS) to prevent insulin resistance. In L6 cells, mitoNEET prevented insulin resistance via regulation of mitochondrial iron, ROS, and mitochondrial fission.