Proline dehydrogenase 1 (PRODH) (PRODH)

Proline dehydrogenase 1 (PRODH), also known as proline oxidase, is a mitochondrial inner membrane enzyme that catalyzes the first and rate-limiting step of proline catabolism by converting L-proline to delta-1-pyrroline-5-carboxylate [1, 3]. This enzymatic step is a critical component of the proline cycle, which links amino acid metabolism to the mitochondrial electron transport chain for ATP production and the generation of reactive oxygen species (ROS) [4, 5, 12]. In oncology, PRODH plays a dichotomous role; it can act as a p53-induced tumor suppressor by promoting ROS-mediated apoptosis or as an oncogene by supporting cancer cell survival and metabolic anaplerosis under environmental stress conditions [1, 3, 8, 17]. Consequently, PRODH has emerged as a promising therapeutic target for disrupting metabolic reprogramming in various cancers, including breast, renal, and lung malignancies [3, 5, 12]. Drug discovery efforts focus on both reversible and irreversible inhibitors, such as N-propargylglycine, which aim to exploit synthetic lethal vulnerabilities in tumor cells, particularly in combination with other metabolic inhibitors [11, 14, 17]. Beyond its role in cancer, PRODH is significant in neurobiology as its gene is located within the 22q11.2 deletion syndrome region, and its dysfunction is associated with schizophrenia and impaired glutamatergic signaling [4, 11, 14].

Other names

Proline oxidasePOXPRODH1PIG6HSPOXProline dehydrogenase, mitochondrial

Suicide or reversible inhibition of the mitochondrial enzyme proline dehydrogenase, preventing the oxidation of proline to delta-1-pyrroline-5-carboxylate and thereby disrupting cancer cell ATP production and ROS signaling pathways essential for survival under metabolic stress [1, 12, 17].