Endonuclease G, mitochondrial (ENDOG)

Endonuclease G, mitochondrial (ENDOG or EndoG), is a nuclear-encoded enzyme primarily localized to the mitochondrial intermembrane space, belonging to the non-specific ββα-Me-finger nuclease family[1][4][5]. It plays a key role in **caspase-independent apoptosis** by translocating to the nucleus under oxidative stress, where it mediates large-scale chromatin DNA degradation, contributing to cell death[1][2][4]. ENDOG also has physiological nuclear functions, participating in site-specific DNA cleavage during replication stress, and supports **mitochondrial DNA replication** by generating RNA primers for DNA polymerase gamma[3][5]. It cleaves both DNA and RNA, with preference for GC-rich sequence tracts, and its action is enhanced during oxidative and replication stress, where it helps remove damaged mitochondrial DNA (mtDNA), thus maintaining mitochondrial DNA integrity and cellular homeostasis[1][5]. Aberrant regulation or mutation of ENDOG is linked to various human diseases such as **cancer**, **aging**, **Parkinson’s disease**, and metabolic/liver disorders[1][3][5]. ENDOG is considered a current or potential **therapeutic target** due to its central role in apoptosis and mitochondrial genome regulation, but drug modulators are not yet established in clinical use. **Note**: No clinical or established drugs currently target ENDOG directly and it is not considered a routine clinical biomarker. Its safety profile as a therapeutic target remains under investigation, primarily due to the risks inherent in manipulating apoptotic and mitochondrial pathways[1][5].

Other names

EndoGendonuclease Gmitochondrial endonuclease GENDOGEndo G