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.
12 affiliations
- 1Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
- 2Department of Plastic and Reconstructive Surgery, E-Da Hospital, Kaohsiung, 82445, Taiwan.
- 3Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
- 4Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan.
- 5Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833401, Taiwan.
- 6Department of Nutrition and Health Science, Fooyin University, Kaohsiung, 83102, Taiwan.
- 7Department of Nursing, Asia University, Taichung, 413305, Taiwan.
- 8Division 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. [email protected].
- 9Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833401, Taiwan. [email protected].
- 10Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833401, Taiwan. [email protected].
- 11Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404333, Taiwan. [email protected].
- 12School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333323, Taiwan. [email protected].
Abstract
Background
This 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
The 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
The activation of the AMPK-Mfn2 axis protected the testis against TTIR injury.
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BibTeX
@article{chen2026mitofusin2,
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.}},
author = {Yen-Ta Chen and Jui-Po Yeh and Yei-Tsung Chen and Yi-Ling Chen and Yi-Ting Wang and Chi-Ruei Huang and Pei-Lin Shao and Chih-Chao Yang and Hon-Kan Yip},
journal = {Stem cell research \& therapy},
year = {2026},
month = aug,
doi = {10.1186/s13287-026-05196-x},
url = {https://europepmc.org/article/MED/42972475},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 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.
AU - Yen-Ta Chen
AU - Jui-Po Yeh
AU - Yei-Tsung Chen
AU - Yi-Ling Chen
AU - Yi-Ting Wang
AU - Chi-Ruei Huang
AU - Pei-Lin Shao
AU - Chih-Chao Yang
AU - Hon-Kan Yip
PY - 2026
DA - 2026/08/04
JO - Stem cell research & therapy
DO - 10.1186/s13287-026-05196-x
UR - https://europepmc.org/article/MED/42972475
AB - Background This 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 The 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 The activation of the AMPK-Mfn2 axis protected the testis against TTIR injury.
SN - 1757-6512
ER -