Evaluation of bioenergetic and mitochondrial function in liver transplantation. Martins Rui Miguel,Teodoro João Soeiro,Furtado Emanuel,Rolo Anabela Pinto,Palmeira Carlos Marques,Tralhão José Guilherme Clinical and molecular hepatology BACKGROUND/AIMS:We measured changes in mitochondrial function and bioenergetics that occur during ischemia/ reperfusion in fresh liver samples of patients undergoing liver transplantation. These variations correlated with markers of liver function and clinical outcome. Ischemia/reperfusion injury related to liver transplantation affects mitochondrial function and bioenergetics. Experimental studies were conducted to identify the role of bioenergetics and mitochondrial dysfunction. To the best of our knowledge, no investigation of these two factors' impacts on liver transplantation has been performed. METHODS:This was a prospective study of 28 patients who underwent liver transplantation. We measured parameters of mitochondrial function and bioenergetics in biopsies performed during the procedure. RESULTS:We observed a statistically significant reduction in mitochondrial membrane potential, an increase in lag phase, and decreases in mitochondrial respiration and adenosine triphosphate content (P<0.010). Higher postoperative aminotransferase peaks correlated with worse mitochondrial function; mitochondrial respiration correlated with arterial lactate (P<0.010). CONCLUSION:There is a relationship between mitochondrial function and ischemia/reperfusion injury. The future use of these clinical markers as prognostic factors may allow early identification of post-transplant liver failure and may indicate the need to perform a new transplant. 10.3350/cmh.2018.0087

Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer. Chang Jui-Chih,Chang Huei-Shin,Wu Yao-Chung,Cheng Wen-Ling,Lin Ta-Tsung,Chang Hui-Ju,Kuo Shou-Jen,Chen Shou-Tung,Liu Chin-San Journal of experimental & clinical cancer research : CR BACKGROUND:The transfer of whole mitochondria that occurs during cell contact has been found to support cancer progression. However, the regulatory role of mitochondria alone is difficult to elucidate due to the complex microenvironment. Currently, mitochondrial transplantation is an available approach for restoring mitochondrial function in mitochondrial diseases but remains unclear in breast cancer. Herein, effects of mitochondrial transplantation via different approaches in breast cancer were investigated. METHODS:Whole mitochondria (approximately 10.5 μg/ml) were transported into MCF-7 breast cancer cells via passive uptake or Pep-1-mediated delivery. Fresh mitochondria isolated from homeoplasmic 143B osteosarcoma cybrids containing mitochondrial DNA (mtDNA) derived from health individuals (Mito) or mtDNA with the A8344G mutation (Mito) were conjugated with cell-penetrating peptide Pep-1 (P-Mito) or not conjugated prior to cell co-culture. Before isolation, mitochondria were stained with MitoTracker dye as the tracking label. After 3 days of treatment, cell viability, proliferation, oxidative stress, drug sensitivity to Doxorubicin/Paclitaxel and mitochondrial function were assessed. RESULTS:Compared with P-Mito, a small portion of Mito adhered to the cell membrane, and this was accompanied by a slightly lower fluorescent signal by foreign mitochondria in MCF-7 cells. Both transplantations induced cell apoptosis by increasing the nuclear translocation of apoptosis-inducing factor; inhibited cell growth and decreased oxidative stress in MCF-7 cells; and increased the cellular susceptibility of both the MCF-7 and MDA-MB-231 cell lines to Doxorubicin and Paclitaxel. Mitochondrial transplantation also consistently decreased Drp-1, which resulted in an enhancement of the tubular mitochondrial network, but a distinct machinery through the increase of parkin and mitochondrial fusion proteins was observed in the Mito and P-Mito groups, respectively. Furthermore, although there were no differences in energy metabolism after transplantation of normal mitochondria, metabolism was switched to the energetic and glycolytic phenotypes when the mitochondria were replaced with dysfunctional mitochondria, namely, Mito and P-Mito, due to dramatically induced glycolysis and reduced mitochondrial respiration, respectively. Consequently, transplant-induced growth inhibition was abolished, and cell growth in the Mito group was even higher than that in the control group. CONCLUSION:This study reveals the antitumour potential of mitochondrial transplantation in breast cancer via distinct regulation of mitochondrial function. 10.1186/s13046-019-1028-z

Mitochondrial Transplantation: A Unique Treatment Strategy. Journal of cardiovascular pharmacology ABSTRACT:Mitochondrial transplantation (MT) refers to the process of introducing isolated mitochondria into a damaged area of the heart or other organs. In the past decade, this technique has been continuously updated as the fundamental research on the repair of damaged cells or tissues. In particular, in the field of heart protection from ischemia-reperfusion injury, the MT therapy has been developed to the clinical trial stage. Generally speaking, the goal of therapeutic intervention is to replace damaged mitochondria or increase the transfer of mitochondria between cells so as to improve mitochondrial dysfunction. In this review, we summarized the studies on MT conducted at different time nodes and outlined a range of different methods for delivering mitochondria into the target site. Finally, we described the applications of MT in different diseases and discussed the clinical studies of human MT currently in progress and the problems that need to be overcome. We hope to provide new ideas for the treatment of mitochondrial defect-related diseases. 10.1097/FJC.0000000000001247

Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases. Journal of translational medicine Cardiovascular disease (CVD) is the leading cause of noncommunicable disease-related death worldwide, and effective therapeutic strategies against CVD are urgently needed. Mitochondria dysfunction involves in the onset and development of CVD. Nowadays, mitochondrial transplantation, an alternative treatment aimed at increasing mitochondrial number and improving mitochondrial function, has been emerged with great therapeutic potential. Substantial evidence indicates that mitochondrial transplantation improves cardiac function and outcomes in patients with CVD. Therefore, mitochondrial transplantation has profound implications in the prevention and treatment of CVD. Here, we review the mitochondrial abnormalities that occur in CVD and summarize the therapeutic strategies of mitochondrial transplantation for CVD. 10.1186/s12967-023-04203-6

Mitochondrial transplantation for organ rescue. Mitochondrion Mitochondrial transplantation involves the replacement or augmentation of native mitochondria damaged, by ischemia, with viable, respiration-competent mitochondria isolated from non-ischemic tissue obtained from the patient's own body. The uptake and cellular functional integration of the transplanted mitochondria appears to occur in all cell types. Efficacy and safety have been demonstrated in cell culture, isolated perfused organ, in vivo large animal studies and in a first-human clinical study. Herein, we review our findings and provide insight for use in the treatment of organ ischemia- reperfusion injury. 10.1016/j.mito.2022.02.007