EndoG, also known as endonuclease G, is a nuclear-encoded mitochondrial-localized nuclease. It is involved in multiple biological processes such as apoptosis, autophagy, and mitochondrial DNA (mtDNA) maintenance. In apoptosis, it translocates to the nucleus to participate in DNA fragmentation; in autophagy, it can be released from mitochondria to promote this process through various signaling pathways, like being phosphorylated by GSK3B to initiate autophagy [1,2].

In a patient with mitochondrial myopathy and multiple mtDNA deletions, biallelic variants in ENDOG were identified, suggesting its role in mtDNA maintenance [3]. In tumor models, reducing ENDOG expression hindered the growth of some tumors with low PTEN activity and high p-AKT expression, indicating its prognostic value in certain cancers [4]. Autophagy restricts mtDNA damage-induced release of ENDOG to regulate genome stability, as suppression of autophagy causes ENDOG to translocate to nuclei and sustain nDNA damage [5].

In conclusion, EndoG plays essential roles in apoptosis, autophagy, mtDNA maintenance, and tumor cell proliferation. Studies on EndoG, especially through gene-variant-associated patient cases and in-vivo models like tumor models, contribute to understanding its functions in disease conditions such as mitochondrial myopathy and certain cancers.

References:

1. Li, Jianshuang, Wang, Wenjun, Zhou, Qinghua. 2021. Conserved role of ENDOG in promoting autophagy. In Autophagy, 17, 1061-1062. doi:10.1080/15548627.2021.1907513. https://pubmed.ncbi.nlm.nih.gov/33779488/

2. Wang, Wenjun, Li, Jianshuang, Zhou, Qinghua. 2024. The biological function of cytoplasm-translocated ENDOG (endonuclease G). In Autophagy, 20, 445-447. doi:10.1080/15548627.2023.2271750. https://pubmed.ncbi.nlm.nih.gov/37889084/

3. Nasca, Alessia, Legati, Andrea, Meneri, Megi, Ronchi, Dario, Ghezzi, Daniele. 2022. Biallelic Variants in ENDOG Associated with Mitochondrial Myopathy and Multiple mtDNA Deletions. In Cells, 11, . doi:10.3390/cells11060974. https://pubmed.ncbi.nlm.nih.gov/35326425/

4. Barés, Gisel, Beà, Aida, Hernández, Luís, Dolcet, Xavier, Sanchis, Daniel. 2021. ENDOG Impacts on Tumor Cell Proliferation and Tumor Prognosis in the Context of PI3K/PTEN Pathway Status. In Cancers, 13, . doi:10.3390/cancers13153803. https://pubmed.ncbi.nlm.nih.gov/34359707/

5. Chao, Tung, Shih, Hsueh-Tzu, Hsu, Shih-Chin, Tsai, Ting-Fen, Chang, Zee-Fen. 2021. Autophagy restricts mitochondrial DNA damage-induced release of ENDOG (endonuclease G) to regulate genome stability. In Autophagy, 17, 3444-3460. doi:10.1080/15548627.2021.1874209. https://pubmed.ncbi.nlm.nih.gov/33465003/