PRODH, also known as proline dehydrogenase or proline oxidase, is a mitochondria-localized enzyme involved in proline metabolism. It catalyzes the conversion of proline into pyrroline-5-carboxylate, a process that can produce either ATP or reactive oxygen species (ROS), thereby influencing cell survival or death. This enzyme is associated with multiple biological pathways, including energy metabolism, apoptosis, autophagy, and is important for maintaining cellular homeostasis [3,4,5,7].

In breast cancer cells, PRODH expression is reduced in tamoxifen-resistant cells. Overexpression of PRODH enhances tamoxifen response both in vitro and in vivo, while knockdown confers tamoxifen resistance in sensitive cells. Mechanistically, PRODH regulates tamoxifen resistance by modulating ferroptosis in these cells [1]. In naive human embryonic stem cells (hESCs), PRODH is upregulated compared to primed counterparts. Its knockdown promotes mitochondrial oxidative phosphorylation and ROS production, triggering autophagy, DNA damage, and apoptosis, suggesting it safeguards naive pluripotency by limiting excessive ROS [2]. In MCF-7 breast cancer cells, drugs like celecoxib and metformin induce apoptosis through upregulation of PRODH/POX [3,4]. In the heart, PRODH expression is suppressed after transverse aortic constriction (TAC). Cardiac-specific PRODH knockout mice show worsened cardiac dysfunction, while overexpression has a protective effect, indicating its role in modulating cardiac remodeling [6].

In conclusion, PRODH plays essential roles in multiple biological processes, including cell survival, pluripotency maintenance, and cardiac function. Studies using gene knockout models, such as in breast cancer, hESCs, and the heart, have revealed its significance in various disease-related contexts. These findings highlight the potential of PRODH as a therapeutic target in treating diseases like breast cancer and cardiac remodeling.