Mitochondrial transplantation: A promising therapy for mitochondrial disorders

Jiao, Qiangqiang; Xiang, Li; Chen, Yuping

doi:10.1016/j.ijpharm.2024.124194

International Journal of Pharmaceutics

2024

DOI: 10.1016/j.ijpharm.2024.124194

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Mitochondrial transplantation: A promising therapy for mitochondrial disorders

Qiangqiang Jiao,

Li Xiang,

Yuping Chen

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2024

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Cited by 5 publications

References 145 publications

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Mitochondrial transplantation reconstructs the oxidative microenvironment within fibroblasts to reverse photoaging

Lu,

Zhang,

et al. 2024

Biochemical and Biophysical Research Communications

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Mitochondrial transplantation reconstructs the oxidative microenvironment within fibroblasts to reverse photoaging

Lu,

Zhang,

et al. 2024

Biochemical and Biophysical Research Communications

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Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model

Yazdani,

Yang,

Haykal

et al. 2024

Transplantation

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Background. Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation. Methods. Donor C57BL/6 mice underwent ExT via treadmill running or remained sedentary. After 4 wk, the donor liver underwent cold storage and subsequent orthotopic liver transplantation or ex vivo warm reperfusion. Results. Donor liver from mice subjected to ExT showed significantly decreased hepatic injury on reperfusion. Tissue histology revealed decreased sinusoidal congestion, vacuolization, and hepatocellular necrosis in livers from ExT mice, and immunofluorescence staining further revealed a decreased number of apoptotic cells in ExT grafts. Livers from ExT donors expressed decreased intragraft inflammatory cytokines cascade, decreased neutrophil infiltration and neutrophil extracellular traps, and increased M2 phenotype of recipient macrophages compared with grafts from sedentary mice. After cold storage, liver grafts from ExT donors showed decreased accumulation of reactive oxygen species and decreased levels of cytochrome c and high mobility group box 1 released in the liver effluent. In addition, ExT grafts showed upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and higher levels of mitochondrial content. Similar effects of decreased hepatic injury were observed in wild-type mice when pretreated with a PGC-1α stimulator ZLN005 instead of ExT. Conclusions. These findings suggest that augmenting hepatocytic mitochondrial content through donor exercise or PGC-1α stimulation may offer therapeutic avenues to mitigate postreperfusion inflammation and improve transplant outcomes.

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Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease

Nakano,

Irie,

Matsuo

et al. 2024

J Cereb Blood Flow Metab

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In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.

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Mitochondrial transplantation: A promising therapy for mitochondrial disorders

Cited by 5 publications

References 145 publications

Mitochondrial transplantation reconstructs the oxidative microenvironment within fibroblasts to reverse photoaging

Mitochondrial transplantation reconstructs the oxidative microenvironment within fibroblasts to reverse photoaging

Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model

Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease

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