The role of GOT1 in macrophage function

The role of GOT1 (Glutamic-oxaloacetic transaminase 1) in various cell types has been primarily studied using the inhibitor AOAA (Aminoxyacetic acid), which inhibits GOT1's enzymatic activity. Researchers have generally assumed that the effects observed with AOAA directly reflect the role of GOT1 protein function. However, recent studies, including one discussed in *Nature*, have challenged this assumption, particularly in the context of T cell function. These studies have shown that the phenotypes resulting from AOAA treatment differ significantly from those observed with GOT1 knockdown using retroviral techniques or knockout mice models.

Our recent findings, published in *Communications Biology*, further investigate GOT1's role in macrophages. By employing both knockout and transgenic mouse models in conjunction with AOAA and other GOT1 inhibitors, we discovered that GOT1 is actually dispensable for macrophage function. This conclusion is supported by a comprehensive set of assays performed on macrophages.

Moreover, our research suggests that AOAA may exert pleiotropic effects beyond just targeting GOT1. This observation underscores the necessity of being cautious when interpreting the functional results of specific proteins based solely on inhibitor studies. It highlights the importance of using multiple approaches, such as genetic knockout models, to obtain a more accurate understanding of protein function.

Article link: https://rdcu.be/dMNAr