Arhgap26, also known as GRAF1, is a RhoGAP protein that serves as a putative tumor suppressor gene. It plays crucial roles in multiple biological processes, such as regulating Rho GTPases activity by promoting their hydrolytic ability, and is involved in pathways related to mitochondrial function, actin remodeling, and membrane dynamics [3]. Genetic models, especially knockout mouse models, have been instrumental in studying its functions.

In knockout mouse models, genetic ablation of Arhgap26 led to oocyte death at the GV stage due to mitochondrial dysfunction-induced ROS accumulation. Survived oocytes showed impaired in vitro and in vivo maturation, resulting in maturation arrest, aneuploidy, early embryonic development defects, and subfertility, indicating its role in oocyte quality control and prevention of aneuploidy [1]. In another study, depletion of Arhgap26 in mouse hearts blunted mitochondrial clearance and attenuated compensatory metabolic adaptations to stress, suggesting its importance in maintaining mitochondrial homeostasis [2].

In conclusion, Arhgap26 is essential for maintaining mitochondrial integrity, regulating actin remodeling and membrane dynamics, and ensuring normal oocyte development and fertility. The gene knockout mouse models have significantly contributed to understanding its role in oocyte aneuploidy and mitochondrial-related diseases, providing potential treatment strategies for infertility and heart-related conditions.

References:

1. Li, Sen, Zhang, Yu, Yuan, Ruiying, Wang, Qiang, Xiong, Bo. 2024. ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure. In Cell death and differentiation, 32, 291-305. doi:10.1038/s41418-024-01384-5. https://pubmed.ncbi.nlm.nih.gov/39313581/

2. Zhu, Qiang, Taylor, Joan M. 2024. ARHGAP26/GRAF1 orchestrates actin remodeling and membrane dynamics to drive mitochondrial clearance and promote fuel flexibility. In Autophagy, 20, 1906-1908. doi:10.1080/15548627.2024.2361576. https://pubmed.ncbi.nlm.nih.gov/38855880/

3. Zhang, Lingye, Zhou, Anni, Zhu, Shengtao, Li, Peng, Zhang, Shutian. 2021. The role of GTPase-activating protein ARHGAP26 in human cancers. In Molecular and cellular biochemistry, 477, 319-326. doi:10.1007/s11010-021-04274-3. https://pubmed.ncbi.nlm.nih.gov/34716859/