Proline dehydrogenase 1, mitochondrial (PRODH)

Proline dehydrogenase 1, mitochondrial (PRODH), also known as proline oxidase, is a FAD-dependent enzyme located on the inner mitochondrial membrane that catalyzes the first step of proline catabolism: the oxidation of L-proline to (S)-1-pyrroline-5-carboxylate (P5C)[1][6][7][8]. In this redox reaction, electrons from proline reduce FAD to FADH2, which then feeds into the mitochondrial electron transport chain, linking proline metabolism to cellular ATP production and reactive oxygen species (ROS) generation[1][7][8]. PRODH is encoded by the PRODH gene on chromosome 22 (in humans) and is distinct from PRODH2, which oxidizes trans-4-hydroxy-L-proline[7]. PRODH activity is essential for maintaining amino acid pools, cellular redox balance, and adaptive responses to stress[1][3][4][8]. Clinically, loss-of-function mutations in PRODH result in hyperprolinemia type I, which ranges from asymptomatic to neurologic manifestations (e.g., seizures, cognitive deficits), and genetic variation in PRODH has been implicated in susceptibility to schizophrenia and other psychiatric disorders[3][5]. In cancer biology, PRODH-driven proline metabolism can promote either apoptosis (through ROS generation) or tumor growth and immune suppression, depending on context[4][7][8]. Currently, no specific drugs are approved to directly modulate PRODH in humans, but it remains a potential therapeutic target in oncology and immunology[7].

Other names

Proline oxidasePRODH1PutA (in bacteria)POX

Drugs would modulate proline oxidation, alter ROS production, disrupt redox homeostasis, and influence cell proliferation or death pathways, depending on inhibition or activation[7][8].