Mitochondrial transplantation reduces lower limb ischemia-reperfusion injury by increasing skeletal muscle energy and adipocyte browning

Jiaqi Zeng; Jianing Liu; Haiya Ni; Ling Zhang; Jun Wang; Yazhou Li; Wentao Jiang; Ziyu Wu; Min Zhou

doi:10.1016/j.omtm.2023.101152

Mitochondrial transplantation reduces lower limb ischemia-reperfusion injury by increasing skeletal muscle energy and adipocyte browning

Mol Ther Methods Clin Dev. 2023 Nov 7:31:101152. doi: 10.1016/j.omtm.2023.101152. eCollection 2023 Dec 14.

Authors

Jiaqi Zeng^{1

2}, Jianing Liu¹, Haiya Ni¹, Ling Zhang¹, Jun Wang¹, Yazhou Li¹, Wentao Jiang³, Ziyu Wu³, Min Zhou^{1

3}

Affiliations

¹ Department of Vascular Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210046, China.
² Department of Vascular Surgery, Kunshan Traditional Chinese Medicine Hospital, Kunshan 215300, China.
³ Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

Abstract

Recent studies have shown that mitochondrial transplantation can repair lower limb IRI, but the underlying mechanism of the repair effect remains unclear. In this study, we found that in addition to being taken up by skeletal muscle cells, human umbilical cord mesenchymal stem cells (hMSCs)-derived mitochondria were also taken up by adipocytes, which was accompanied by an increase in optic atrophy 1 (OPA1) and uncoupling protein 1. Transplantation of hMSCs-derived mitochondria could not only supplement the original damaged mitochondrial function of skeletal muscle, but also promote adipocyte browning by increasing the expression of OPA1. In this process, mitochondrial transplantation can reduce cell apoptosis and repair muscle tissue, which promotes the recovery of motor function in vivo. To the best of our knowledge, there is no study on the therapeutic mechanism of mitochondrial transplantation from this perspective, which could provide a theoretical basis.

Keywords: Mitochondrial damage; adipocyte browning; lower limb ischemia-reperfusion injury; mesenchymal stem cells; mitochondrial transplantation.