Lin F, Ma KX, Liang XT. Insights into mitofusin-2 and endoplasmic reticulum stress regulation in adipose-derived mesenchymal stem cells senescence. World J Stem Cells 2025; 17(11): 112476 [DOI: 10.4252/wjsc.v17.i11.112476]
Corresponding Author of This Article
Xiao-Ting Liang, MD, PhD, Associate Researcher, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. liangxt@tongji.edu.cn
Research Domain of This Article
Cell Biology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Nov 26, 2025 (publication date) through Nov 26, 2025
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Stem Cells
ISSN
1948-0210
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Lin F, Ma KX, Liang XT. Insights into mitofusin-2 and endoplasmic reticulum stress regulation in adipose-derived mesenchymal stem cells senescence. World J Stem Cells 2025; 17(11): 112476 [DOI: 10.4252/wjsc.v17.i11.112476]
World J Stem Cells. Nov 26, 2025; 17(11): 112476 Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.112476
Insights into mitofusin-2 and endoplasmic reticulum stress regulation in adipose-derived mesenchymal stem cells senescence
Fang Lin, Ke-Xin Ma, Xiao-Ting Liang
Fang Lin, Ke-Xin Ma, Xiao-Ting Liang, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Xiao-Ting Liang, Institute for Regenerative Medicine, Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen 518025, Guangdong Province, China
Author contributions: Lin F drafted the manuscript and conducted the literature analysis; Ma KX participated in revision of the content and contributed to institutional coordination; Liang XT conceived the concept, supervised the project, and provided final approval of the version to be submitted. All authors reviewed and approved the final manuscript.
Supported by Shenzhen Science and Technology Program, No. JCYJ20240813162036046.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ting Liang, MD, PhD, Associate Researcher, Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, No. 150 Jimo Road, Shanghai 200120, China. liangxt@tongji.edu.cn
Received: July 28, 2025 Revised: September 16, 2025 Accepted: October 20, 2025 Published online: November 26, 2025 Processing time: 120 Days and 22.3 Hours
Abstract
This article comments on the study by Fang, which demonstrates that reduced nuclear factor erythroid-derived 2 (NRF2) activity promotes endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells from hypertrophic obese mice, primarily through downregulation of mitofusin-2 (MFN2). Robust methodologies, including knockdown/rescue experiments, chromatin immunoprecipitation quantitative polymerase chain reaction, co-immunoprecipitation, and transplantation assays, substantiate that NRF2 or MFN2 disruption impairs the therapeutic potential of these cells in insulin resistance. However, the proposed MFN2-binding immunoglobulin protein interaction remains indirectly supported and requires biochemical validation (e.g., glutathione S-transferase pull-down/Forster resonance energy transfer/cross-linking mass spectrometry). Moreover, NRF2 may influence endoplasmic reticulum stress and senescence through additional unexplored targets. Future studies should clarify the structural and functional nature of the MFN2-binding immunoglobulin protein relationship and its implications for mitochondrial dynamics, endoplasmic reticulum-mitochondria tethering, and calcium signaling.
Core Tip: Fang’s study links the nuclear factor erythroid-derived 2-mitofusin-2 (MFN2) axis to endoplasmic reticulum stress and senescence in adipose-derived mesenchymal stem cells from obese mice. While the evidence for reduced nuclear factor erythroid-derived 2 and MFN2 suppression is compelling, key issues remain. The specific function of MFN2 in aging adipose-derived mesenchymal stem cells, its potential interaction with binding immunoglobulin protein, and its influence on endoplasmic reticulum stress remain unresolved. Future studies should elucidate the role of MFN2, establish direct biochemical evidence, and assess the therapeutic relevance of targeting this axis in insulin resistance using diet-induced obesity models.
