Subcellular distribution of prohibitin in rat liver during liver regeneration and its cellular implication

Abstract Introduction and Objectives: Little is known about Prohibitin (Phb1)’s role during liver regeneration (LR). Previously, we found that the expression of Phb1 was down-regulated in rat liver mitochondria at 24 h after 70% partial hepatectomy (PHx) based on subcellular proteomic analysis. Here, we further explored the potential role of Phb1 during LR. Materials and Methods The changes in the expression of mRNA and protein levels, subcellular distribution and abundance of Phb1 in rat liver during LR were observed after 70% PHx. Mitochondrial alterations and the level of apoptosis were observed through electron microscopy and flow cytometry. RNA interference-mediated knockdown of Phb1 (PHBi) was carried out in BRL-3A cells. Results Comparing with sham-operation control groups, Phb1 mRNA and protein levels were down-regulated at 24 h, up-regulated at 72 h and 168 h in 70% PHx test groups. Phb1 was mainly located in mitochondria, where its abundance was reduced at 24 h, significantly increased at 72 h and almost recovered to normal at 168 h. Phb1 was also located in nucleus, where its abundance was increased continuously 72 h and 168 hours after 70% PHx.. The altered ultrastructure and reduced mass of mitochondria during LR were nearly recovered to normal at 168 h. PHBi in BRL-3A cells resulted in increased S-phase entry as well as the number of apoptotic cells, and disruption of mitochondrial membrane potential. Conclusions Phb1 may play a role both in maintaining mitochondrial stabilization and in regulating cell proliferation and apoptosis of rat liver cells during LR.