{ "abstract": "Background\n\nThis study tested the hypothesis that mitofusin-2 overexpression (Mfn2Ove) in adipose-derived mesenchymal stem cells (ADMSCOve-Mfn2) protects the testis against testicular torsion-induced ischemia‒reperfusion (TTIR) injury via AMP-activated protein kinase (AMPK)-mediated mitochondrial dynamic homeostasis.Methods and results\n\nThe in vitro results revealed that Mfn2Ove significantly increased cell viability/mitochondrial content/fusion protein/ATP levels (all P < 0.001). Mfn2Ove in ADMSCs and GC-1 cells upregulated the expression of mitochondrial fusion proteins/content/OXPHOS complexes/p-AMPK and suppressed fission proteins/autophagy/oxidative stress, which were reversed by siRNA-Mfn2 (all P < 0.001). Compared with the control, Mfn2Ove significantly increased mitochondrial length in ADMSCs and GC-1 cells (P < 0.0001). IR activated p-AMPK and upregulated fission proteins, whereas the AMPK inhibitor did not reverse the ability of Mfn2Ove to upregulate p-AMPK/Mfn2/OPA1/OXPHOS/mitochondrial length in ADMSCs and GC-1 cells (P < 0.0001). By day 28 after TTIR induction, testicular protein levels of oxidative stress/fibrosis/apoptosis/autophagy/DNA-damage/fission were significantly increased in group 2 (TTIR) compared with those of group 1 (sham-control), whereas the protein levels of mitochondrial fusion/OXPHOS exhibited an opposite pattern of oxidative stress between groups 1 and 2 that were significantly reversed by AMDCs (group 3) and further reversed by ADMSCOVe-Mfn2 (group 4), which was reversed by siRNA-Mfn2 in ADMSCs (group 5) (all P < 0.00001). The p-AMPK protein level significantly increased from groups 1 to 4 but was reversed in group 5 (all P < 0.00001). The cellular levels of androgen receptor/Sertoli cells/alpha-microtubule/vimentin/testis injury score showed identical patterns to those of OXPHOS complexes among the groups (all P < 0.00001).Conclusion\n\nThe activation of the AMPK-Mfn2 axis protected the testis against TTIR injury.", "abstract_shown": true, "affiliations": [ "Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.", "Department of Plastic and Reconstructive Surgery, E-Da Hospital, Kaohsiung, 82445, Taiwan.", "Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.", "Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan.", "Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833401, Taiwan.", "Department of Nutrition and Health Science, Fooyin University, Kaohsiung, 83102, Taiwan.", "Department of Nursing, Asia University, Taichung, 413305, Taiwan.", "Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123, Dapi Road, Niaosung Dist., Kaohsiung, 83301, Taiwan. papaofison@gmail.com.", "Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. han.gung@msa.hinet.net.", "Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833401, Taiwan. han.gung@msa.hinet.net.", "Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404333, Taiwan. han.gung@msa.hinet.net.", "School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333323, Taiwan. han.gung@msa.hinet.net." ], "article_type": "research article", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0 ], "name": "Yen-Ta Chen" }, { "affs": [ 1 ], "name": "Jui-Po Yeh" }, { "affs": [ 2 ], "name": "Yei-Tsung Chen" }, { "affs": [ 3, 4, 5 ], "name": "Yi-Ling Chen" }, { "affs": [ 3, 4 ], "name": "Yi-Ting Wang" }, { "affs": [ 3 ], "name": "Chi-Ruei Huang" }, { "affs": [ 6 ], "name": "Pei-Lin Shao" }, { "affs": [ 7 ], "name": "Chih-Chao Yang" }, { "affs": [ 8, 9, 10, 11 ], "name": "Hon-Kan Yip", "orcid": "0000-0002-6305-5717" } ], "bibtex": "https://research.draconitic.com/paper/bf0f1y36sy9re.bib", "cited_by": 0, "doi": "10.1186/s13287-026-05196-x", "fulltext_url": "https://europepmc.org/articles/PMC13725951", "id": "bf0f1y36sy9re", "issns": [ "1757-6512" ], "landing_url": "https://europepmc.org/article/MED/42972475", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "openalex", "1312|Mitochondrial Function and Pathology" ] ], "openalex": "W7172407169", "pdf_url": "https://europepmc.org/articles/PMC13725951?pdf=render", "pmcid": "PMC13725951", "pmid": "42972475", "published": "2026-08-04", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/bf0f1y36sy9re.ris", "sources": [ { "first_seen": "2026-11-04T15:20:45Z", "native_id": "MED:42972475", "source": "europepmc", "url": "https://europepmc.org/article/MED/42972475" }, { "first_seen": "2026-11-05T12:22:23Z", "native_id": "PMC13725951", "source": "pmc", "url": "https://doi.org/10.1186/s13287-026-05196-x" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Mitochondrial Function and Pathology", "subfield": "molecular-biology" } ], "title": "Mitofusin-2 overexpression in adipose tissue-derived mesenchymal stem cells protects the testis against testicular torsion-induced ischemia-reperfusion injury through preservation of mitochondrial homeostasis associated with AMPK activation.", "title_text": "Mitofusin-2 overexpression in adipose tissue-derived mesenchymal stem cells protects the testis against testicular torsion-induced ischemia-reperfusion injury through preservation of mitochondrial homeostasis associated with AMPK activation.", "type": "peer-reviewed", "updated_at": "2026-11-06T12:22:01Z", "url": "https://research.draconitic.com/paper/bf0f1y36sy9re", "venue": "Stem cell research & therapy", "versions": [] }