Phb2-KO Mouse

Phb2, also known as prohibitin 2, is a highly conserved membrane scaffold protein. It plays a crucial role in mitochondrial quality control, especially in mitophagy, the process of selectively removing damaged mitochondria. It is involved in the PHB2-PARL-PGAM5-PINK1 axis, which is a novel pathway of PHB2-mediated mitophagy [1]. Additionally, it has implications in cellular energy metabolism, with a potential role in regulating oxidative phosphorylation (OXPHOS) [2].

Knockdown of Phb2 in various cell models has provided insights into its functions. In colorectal cancer cells, Phb2 knockdown significantly reduces mitochondrial OXPHOS levels, suggesting its role in promoting cell proliferation and tumorigenesis through enhancing OXPHOS [2]. In gastric cancer cells, silencing Phb2 reduces cell proliferation and retards tumour growth, as Phb2 promotes cell proliferation via the PI3K/Akt signaling pathway by degrading SHIP2 through the E3 ligase NEDD4 [3]. In hepatocellular carcinoma, the lncRNA-encoded peptide PINT87aa can reduce Phb2 expression by blocking FOXM1-mediated Phb2, inducing cellular senescence and decreasing mitophagy [4].

In conclusion, Phb2 is essential for mitochondrial function, particularly in mitophagy and energy metabolism. Findings from gene-knockdown studies in different cancer cell models, such as colorectal, gastric, and hepatocellular carcinoma, highlight its role in cancer development. These studies provide valuable insights into the molecular mechanisms underlying cancer progression, suggesting Phb2 as a potential therapeutic target in these disease areas.

References:

1. Yan, Chaojun, Gong, Longlong, Chen, Li, Désaubry, Laurent, Song, Zhiyin. 2019. PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis. In Autophagy, 16, 419-434. doi:10.1080/15548627.2019.1628520. https://pubmed.ncbi.nlm.nih.gov/31177901/

2. Ren, Lin, Meng, Li, Gao, Jing, Rong, Ziye, Ye, Yan. 2023. PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation. In Cell death & disease, 14, 44. doi:10.1038/s41419-023-05575-9. https://pubmed.ncbi.nlm.nih.gov/36658121/

3. Xu, Liang, Xiang, Wanying, Yang, Jiezhen, Jin, Lei, Ye, Yan. 2024. PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer. In Journal of experimental & clinical cancer research : CR, 43, 17. doi:10.1186/s13046-023-02937-1. https://pubmed.ncbi.nlm.nih.gov/38200519/

4. Xiang, Xiaohong, Fu, Yunong, Zhao, Kun, Zhang, Nu, Qu, Kai. 2021. Cellular senescence in hepatocellular carcinoma induced by a long non-coding RNA-encoded peptide PINT87aa by blocking FOXM1-mediated PHB2. In Theranostics, 11, 4929-4944. doi:10.7150/thno.55672. https://pubmed.ncbi.nlm.nih.gov/33754036/