Autologous mitochondrial transplantation in male mice as a strategy to prevent deleterious effects of peripheral ischemia-reperfusion

Ischemia-reperfusion (IR) is known to induce severe tissue damage, notably through mitochondrial dysfunction. Mitochondrial transplantation has emerged as a promising therapeutic strategy in cardiac IR; however, few studies have previously assessed its efficacy in the context of peripheral IR. Therefore, the objective of this study was to assess the effect of mitochondrial transplantation in a hindlimb model of IR injury. Thirty-six SWISS mice were divided into three groups: control (CTL, n = 12), ischemia-reperfusion (IR, n = 12), and IR with mitochondrial transplantation (MT, n = 12). Ischemia (2 h) was induced using the tourniquet model around the right hind limb in the IR and MT groups. In MT group, mitochondria isolated from the right rectus muscle, a nonischemic region, were injected shortly before reperfusion. Mitochondrial respiration, calcium retention capacity, and Western blotting analysis were performed 2 h after reperfusion. Compared with the CTL group, IR led to a decrease in the mitochondrial respiratory capacity, particularly for the basal state (-30%; P = 0.015), oxidative phosphorylation (-36%; P = 0.024), and calcium retention capacity (-45%; P = 0.007). Interestingly, mitochondrial transplantation partially restored these functions since no differences between MT and CTL groups were found. In addition, the administration of healthy mitochondria resulted in a positive regulation of redox balance and mitochondrial dynamics within the skeletal muscle. Although further investigations are needed to better characterize underlying mechanisms, mitochondrial transplantation represents a promising strategy in the setting of IR-induced muscular damage.