Phb1-KO Mouse

Phb1, also known as prohibitin 1, is a multifunctional chaperone/scaffold protein. It assembles with Phb2 at the mitochondrial inner membrane to form a multi-dimer complex, playing crucial roles in various mitochondrial functions, such as aging, proliferation, and in degenerative and metabolic diseases [3,4]. It is also involved in regulating innate immune responses, cell apoptosis, and cancer-related processes [1,5,2].

In terms of functional studies, in macrophages, loss of Phb1 leads to increased interleukin-1β (IL-1β) levels, cytoplasmic release of mtDNA, and inflammatory responses [1]. Phb1-deficient macrophages, serum from myeloid-specific Phb1 KO (Phb1MyeKO) mice, and peripheral blood mononuclear cells from neonatal sepsis patients all show these phenotypes, and Phb1 KO mice are intolerant of lipopolysaccharide shock [1]. In castration-resistant prostate cancer (CRPC), Phb1 is upregulated and promotes castration resistance of PCa cells under androgen deprivation condition. FL3, a drug targeting Phb1, suppresses CRPC cells both in vitro and in vivo [2].

In conclusion, Phb1 is essential for maintaining mitochondrial integrity and function, and regulating immune responses and cancer-related processes. Studies using Phb1 KO mouse models have significantly enhanced our understanding of its role in inflammatory diseases and cancer, providing potential therapeutic targets for neonatal sepsis and CRPC [1,2].

References:

1. Liu, Hao, Fan, Hualin, He, Pengcheng, Zhao, Guojun, Feng, Du. 2022. Prohibitin 1 regulates mtDNA release and downstream inflammatory responses. In The EMBO journal, 41, e111173. doi:10.15252/embj.2022111173. https://pubmed.ncbi.nlm.nih.gov/36245295/

2. Liu, Junmei, Zhang, Ranran, Su, Tong, Han, Bo, Chen, Weiwen. 2023. Targeting PHB1 to inhibit castration-resistant prostate cancer progression in vitro and in vivo. In Journal of experimental & clinical cancer research : CR, 42, 128. doi:10.1186/s13046-023-02695-0. https://pubmed.ncbi.nlm.nih.gov/37210546/

3. García-Chávez, Diana, Domínguez-Martín, Eunice, Kawasaki, Laura, Funes, Soledad, Coria, Roberto. 2024. Prohibitins, Phb1 and Phb2, function as Atg8 receptors to support yeast mitophagy and also play a negative regulatory role in Atg32 processing. In Autophagy, 20, 2478-2489. doi:10.1080/15548627.2024.2371717. https://pubmed.ncbi.nlm.nih.gov/38964378/

4. Mishra, Suresh. . Phb1:Phb2 heterodimers in the mitochondria-beyond functional interdependence. In The Journal of biological chemistry, 294, 14836. doi:10.1074/jbc.L119.010788. https://pubmed.ncbi.nlm.nih.gov/31586026/

5. Yang, Bo, Lou, Chao, Chen, Shengkai, Zhang, Zhiyuan, Xu, Qin. . XIAP and PHB1 Regulate Anoikis through Competitive Binding to TRAF6. In Molecular cancer research : MCR, 21, 127-139. doi:10.1158/1541-7786.MCR-22-0415. https://pubmed.ncbi.nlm.nih.gov/36346305/