Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2024; 16(1): 65-74
Published online Jan 27, 2024. doi: 10.4254/wjh.v16.i1.65
Subcellular distribution of prohibitin 1 in rat liver during liver regeneration and its cellular implication
Qing-Ju Sun, Tao Liu
Qing-Ju Sun, Department of Clinical Laboratory, Navy No. 971 Hospital, Qingdao 266072, Shandong Province, China
Tao Liu, Department of Infectious Diseases, Navy No. 971 Hospital, Qingdao 266071, Shandong Province, China
Author contributions: Sun QJ designed the research study; Sun QJ and Liu T performed the research; Sun QJ and Liu T analyzed the data and wrote the manuscript; All authors have read and approve the final manuscript.
Institutional review board statement: This study is reported in accordance with the ARRIVE guidelines ( All methods were performed in accordance with the relevant guidelines and regulations.
Institutional animal care and use committee statement: In this study, the ethics approval was obtained from the Medical Research and Ethics Committees at Navy 971 hospital in Qingdao, Shandong, China.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tao Liu, MD, PhD, Doctor, Department of Infectious Diseases, Navy No. 971 Hospital, Qingdao 266071, Shandong Province, China.
Received: September 30, 2023
Peer-review started: September 30, 2023
First decision: October 23, 2023
Revised: November 3, 2023
Accepted: November 28, 2023
Article in press: November 28, 2023
Published online: January 27, 2024
Research background

It is clinically important to develop therapeutic strategies to enhance liver regeneration (LR) or support the liver in its attempt to restore its functional integrity under pathophysiological circumstances. However, the complexity of the regulatory mechanisms of LR, together with our limited understanding of the functional priorities of the hepatocytes have rendered difficult the identification of targets for therapeutic interventions.

Research motivation

Prohibitin 1 (Phb1) is a ubiquitously expressed highly conserved protein among eukaryotes. Previous research has proposed that Phb1 was involved in many cellular processes. Phb1 was reported to mainly localize in mitochondria, with its expression upregulated by mitochondrial stress and downregulated during cellular senescence. Therefore, Phb1 is thought to have a crucial role in mitochondrial function. One study identified a novel function of Phb1 in the maintenance of mitochondrial DNA (mtDNA). In Phb1-knockdown cells, the status of mtDNA is altered in several ways. Despite such information, our understanding of the overall functions of Phb1 in mitochondria remains incomplete and its potential role during LR is largely unexplored. LR is a very complicated biological procedure involving various signal transduction pathways and molecular events. Thus, we hypothesized that Phb1 could play a crucial role during LR.

Research objectives

This study aimed to further investigate the function of Phb1 in mitochondria during changes in Phb1 expression, mitochondrial mass and ultrastructure, and the subcellular distribution of Phb1 at 24, 72 and 168 h post 70% partial hepatectomy (PHx) in rat liver. Using RNA-interference-mediated knockdown of Phb1 (PHBi), we also analyzed the potential functions of Phb1.

Research methods

We examined changes in Phb1 mRNA and protein levels, subcellular distribution, and abundance in rat liver during LR following 70% PHx. We also evaluated mitochondrial changes and apoptosis levels using electron microscopy and flow cytometry. PHBi was performed in BRL-3A cells.

Research results

Compared with sham-operation control groups, Phb1 mRNA and protein levels in 70% PHx test groups were downregulated at 24 h, then upregulated at 72 and 168 h. Phb1 was mainly located in mitochondria, showed a reduced abundance at 24 h, significantly increased at 72 h, and almost recovered to normal at 168 h. Phb1 was also present in nuclei, with continuous increase in abundance observed at 72 and 168 h after 70% PHx. The altered ultrastructure and reduced mass of mitochondria during LR had almost completely recovered to normal at 168 h. PHBi in BRL-3A cells resulted in increased S-phase entry, a higher number of apoptotic cells, and disruption of mitochondrial membrane potential.

Research conclusions

In summary, our results demonstrate that Phb1 plays two roles in the LR process: one is to regulate cell cycle and apoptosis, and the other is to regulate and maintain mitochondrial stability.

Research perspectives

Whether the two effects are directly linked or show two different effects remains unclear. Further in-depth studies will aid in us better understanding the complexities and roles of Phb1 in the LR process.