ENDOG

Endonuclease G, mitochondrial is an is_associated_with::enzyme that in humans is encoded by the ENDOG is_associated_with::gene. This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the mitochondrion to nucleus under oxidative. As a result, EndoG has been implicated in cancer, aging, and neurodegenerative diseases such as Parkinson’s disease (PD). Regulation of its expression levels thus holds potential to treat or ameliorate those conditions.

Function
The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. In some apoptotic pathways, EndoG is released from the mitochondrion and migrates to the nucleus, where it degrades chromatin with the help of other nuclear proteins. In one such pathway, caspase-independent apoptosis, the E3 ligase C terminus of Hsc-70 interacting protein (CHIP), a regulator of EndoG expression, functions as a protective mechanism against oxidative stress. Under normal conditions, EndoG remains bound to Hsp70 and CHIP; however, when undergoing oxidative stress, EndoG dissociates from Hsp70 and CHIP and translocates to the nucleus, where it degrades DNA to effect apoptosis. Therefore, maintaining low levels of EndoG could prevent cell death caused by stress conditions. In addition to DNA degradation, EndoG also stimulates inhibitors of apoptosis proteins (IAPs) to target proteins for proteasomal degradation.

Clinical significance
Previous studies reported greater efficacy of anticancer drugs when used in conjunction with high EndoG levels. Thus, regulators of EndoG, such as CHIP, could serve as therapeutic targets for oxidative stress-induced cell death in cancer and aging. EndoG has also been implicated in Parkinson’s disease (PD), as it induces DNA fragmentation in neurons when translocated from the mitochondria to nuclei. This mechanism involves the kynurenine pathway and the permeability transition pore; as such, targeting molecules in this pathway could prevent EndoG-mediated cell death and effectively help treat PD in patients.