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, a process for selectively removing damaged mitochondria. The PHB2-PARL-PGAM5-PINK1 axis is a novel pathway in PHB2-mediated mitophagy [1]. Additionally, it is involved in cellular energy metabolism, like oxidative phosphorylation, and impacts cell proliferation and tumorigenesis in various cancers [2].

Genetic models, such as gene knockdown experiments, have revealed that PHB2 depletion destabilizes PINK1 in mitochondria, blocking the recruitment of PRKN/Parkin, ubiquitin, and OPTN, thus inhibiting mitophagy [1]. In colorectal cancer, knockdown of PHB2 reduces mitochondrial OXPHOS levels, and it directly interacts with NDUFS1 to enhance complex I activity and promote cell proliferation [2]. In gastric cancer, silencing PHB2 reduces cell proliferation and retards tumor growth [3]. In hepatocellular carcinoma, a peptide PINT87aa can block FOXM1-mediated PHB2, inducing cellular senescence [4].

In conclusion, PHB2 is essential for mitochondrial function and mitophagy. Through model-based research, its role in various cancer-related processes has been identified. These findings contribute to understanding the molecular mechanisms of diseases and suggest PHB2 as a potential therapeutic target for cancer treatment.