Endog

Case study 1: Sumedha Dahal, 2022

Having its genome makes the mitochondrion a unique and semiautonomous organelle within cells. Mapping the deletion junctions suggests that the breakpoints are generally seen at hotspots. '9 bp deletion' (8271-8281). While it is associated with several diseases like myopathy, dystonia, and hepatocellular carcinoma, it has also been used as an evolutionary marker. However, the mechanism responsible for its fragility is unclear.

In the current study, the researchers show that Endonuclease G, a mitochondrial nuclease responsible for nonspecific cleavage of nuclear DNA during apoptosis, can induce breaks at sequences associated with '9 bp deletion' when it is present on a plasmid or in the mitochondrial genome. Through a series of in vitro and intracellular studies, they show that Endonuclease G binds to G-quadruplex structures formed at the hotspot and induces DNA breaks. Therefore, they uncover a new role for Endonuclease G in generating mtDNA deletions, which depends on the formation of G4 DNA within the mitochondrial genome.

Fig1. In vitro nicking assay using purified Endonuclease G on wild type and mutant plasmids containing mitochondrial Region I (pDI1 and pDI2).

Fig2. Localization of Endonuclease G in mitochondria in different cell lines.

Case study 2: Tung Chao, 2021

Genotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage.

The researchers provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released. Furthermore, blocking lysosome function is sufficient to increase the amount of mtDNA leakage to the cytosol, accompanied by ENDOG-free mitochondrial puncta formation with concurrent ENDOG nuclear accumulation. Finally, the researchers showed that HBx, a hepatitis B viral protein capable of suppressing autophagy, also causes mitochondrial permeability-dependent ENDOG mis-localization in nuclei and is linked to hepatitis B virus (HBV)-mediated hepatocellular carcinoma development.

Fig3. The role of ENDOG in nDNA damage. Cells infected with lentivirus of the shRNA of ENDOG for γH2AX IF staining at the time recovery from IR.

Fig4. Effect of TET2 and ENDOG overexpression on nDNA damage. Cells were transfected with GFP or TET2-GFP in combination with ENDOG-GFP plasmids.

Fig1. Proposed model of EndoG-mediated induction of mtDNA OH replication initiation. (Rahel Stefanie Wiehe, 2018)

Fig2. Model depicting ENDOG promotes autophagy through its phosphorylation-mediated interaction with 14-3-3γ and its endonuclease activity-mediated DNA damage response. (Wenjun Wang, 2021)

Endog involved in several pathways and played different roles in them. We selected most pathways Endog participated on our site, such as Apoptosis, which may be useful for your reference. Also, other proteins which involved in the same pathway with Endog were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Endog has several biochemical functions, for example, deoxyribonuclease activity, endonuclease activity, metal ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Endog itself. We selected most functions Endog had, and list some proteins which have the same functions with Endog. You can find most of the proteins on our site.

Endog has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Endog here. Most of them are supplied by our site. Hope this information will be useful for your research of Endog.

DNAJA4; q96be0_human