Pex3, the peroxisomal biogenesis factor 3, is a critical regulator of the peroxisome, an organelle with diverse metabolic functions. Pex3 is involved in peroxisome membrane biogenesis and can recruit other proteins to the peroxisomal membrane, playing roles in processes like autophagy and organelle retention [2]. It is also associated with pathways related to lipid metabolism and stress responses [3]. Genetic models, such as gene knockout mouse models, are valuable for studying its functions.

In Pex3-KO mice, cardiomyocyte-specific knockout results in redox homeostasis imbalance, disrupts endogenous proliferation/development, and impairs myocardial regenerative repair. Mechanistically, Pex3 promotes this repair by affecting plasmalogen metabolism, which activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3 [1]. In another study, conditional knockout in the cochlea of mice revealed that Pex3 is required locally for normal hearing, as its mutation led to early-onset progressive hearing loss and a reduction in inner ear plasmalogens [4].

In conclusion, Pex3 is essential for maintaining normal physiological functions, especially in processes related to redox homeostasis, lipid metabolism, and cell proliferation. The use of Pex3 KO/CKO mouse models has provided insights into its role in myocardial injury repair and hearing, suggesting it could be a potential therapeutic target for related diseases [1,4].

References:

1. Sun, Jia-Teng, Wang, Zi-Mu, Zhou, Liu-Hua, Cui, Yi-Qiang, Wang, Lian-Sheng. 2024. PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3. In Communications biology, 7, 795. doi:10.1038/s42003-024-06483-0. https://pubmed.ncbi.nlm.nih.gov/38951640/

2. Jansen, Renate L M, van der Klei, Ida J. 2019. The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions. In FEBS letters, 593, 457-474. doi:10.1002/1873-3468.13340. https://pubmed.ncbi.nlm.nih.gov/30776093/

3. Cai, Rixin, Tao, Xuelei, Chen, Ying, Cook, Melloni N, Lu, Lu. 2020. Pex3 is involved in the genetic regulation of Nr3c2 expression in the amygdala of mice. In Psychiatry research, 285, 112760. doi:10.1016/j.psychres.2020.112760. https://pubmed.ncbi.nlm.nih.gov/32045820/

4. Kochaj, Rafael M, Martelletti, Elisa, Ingham, Neil J, Lopez-Clavijo, Andrea F, Steel, Karen P. 2022. The Effect of a Pex3 Mutation on Hearing and Lipid Content of the Inner Ear. In Cells, 11, . doi:10.3390/cells11203206. https://pubmed.ncbi.nlm.nih.gov/36291074/