Peptidyl-tRNA hydrolase 2, mitochondrial (PTRH2)

Peptidyl-tRNA hydrolase 2, mitochondrial (PTRH2) is a conserved mitochondrial enzyme with peptidyl-tRNA hydrolase activity, releasing tRNAs from ribosomes during protein synthesis to prevent translational stalling and reduce accumulation of peptidyl-tRNAs, thus supporting protein homeostasis[1][3]. In addition to this core enzymatic function, PTRH2 serves as a key regulator of apoptosis—its release from mitochondria upon cell detachment triggers caspase-independent apoptosis (anoikis) via interactions with transcriptional regulators such as AES and TLE1[1][4]. PTRH2 also mediates prosurvival signals integrin-dependently for ECM-attached cells, modulates the PI3K/AKT and ERK signaling pathways, regulates mitochondrial bioenergetics by interacting with complex I component mt-ND5, and influences muscle development and differentiation[2][3][4]. Pathogenic variants in PTRH2 are linked to a rare recessive disorder, IMNEPD, with neurological, endocrine, and pancreatic involvement, as well as progressive congenital muscle degeneration and multisystem involvement[1][3][4]. PTRH2 disruption is a proposed mechanism in multiple disease states including tumorigenesis, metabolic disorders, and neurodegenerative disease[1][2][3][4]. No small molecules or drugs with direct action on PTRH2 have been described in the current literature, and it is not presently established as a pharmacological biomarker or direct clinical target[1][3][4]. Key references: [1][3][4]

Other names

BIT1Bcl-2 inhibitor of transcription 1PTH2PTH 2Peptidyl-tRNA hydrolase 2CFAP37CGI-147IMNEPDcilia and flagella associated protein 37