Alternative Methods for Mitochondrial Transplantation: Efficiency of Unpackaged and Lipid-Packaged Preparations

Abstract

Mitochondrial transplantation is currently being explored as a means to repair and restore proper organelle function in a variety of inherited and acquired disorders of energy metabolism. The optimal preparation and application of donor mitochondria is unknown, but most studies in vivo have used injection techniques or, for tissue studies, unpackaged mitochondria (organelles isolated and suspended in buffer) in transplant experiments. Packaging in lipid rafts can increase recipient cell uptake of some compounds and objects. We present the first data comparing recipient cell uptake of unpackaged mitochondria to recipient cell uptake of mitochondria packaged in cell membrane lipids. Mitochondria and membranes were prepared from autologous cells and applied to cells (fibroblasts) in culture. Both unpackaged and lipid-packaged mitochondria were taken into recipient cells and the donor mitochondria showed evidence, in each case, of retained functionality and the ability to merge with the recipient mitochondrial matrix. However, lipid packaging appeared to enhance the uptake of functional mitochondria. Current studies of mitochondrial transplantation in animal models might fruitfully explore the utility and efficacy of lipid-packaged mitochondria in transplant experiments.

Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation

“…However, in contrast to intracellular transfer and export/uptake of mitochondria containing EVs, the mechanism by which isolated extracellular mitochondria enter the cell is still obscure. Regardless, transplanted exogenous mitochondria can fuse with the recipient cell’s endogenous mitochondrial network, which in cells results in enhanced cellular respiration and ATP content [ 152 , 153 ]. Attempts have been carried out to increase the penetration efficiency of the exogenous mitochondria.…”

“…In another study, labeling mitochondria with Pep-1, an amphipathic peptide carrier and a member of the cell-penetrating peptide family, significantly increased the efficiency of mitochondrial penetration in pheochromocytoma (PC12) cells and mouse brains treated with 6-hydroxydopamine (6-OHDA), a PD-inducing agent, and in a mitochondrial disease model of myoclonic epilepsy with ragged red fibers. In both models, mitochondrial function was improved [ 152 , 154 ]. The question remains whether artificially increasing mitochondrial penetration is beneficial in all cell types and physiological states, as cellular control on uptake is bypassed.…”

Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells

“…There were several methodologies of mitochondria transplantation reported. One is that mitochondria can be enveloped by lipid vesicles and therefore facilitate the fusion of exogenous mitochondria with target cells [20]. Centrifugation is another method that promote the transplantation of mitochondria, which was first applied in improving the atrophic syndrome [21].…”