The objective of this study is to investigate the influence of exogenous mitochondria (Mt) internalization on the Mt membrane potential of cells. Cationized gelatin nanospheres (cGNS) were prepared to mix Mt at different ratios to prepare Mt associated with cGNS (Mt-cGNS). The Mt internalization depended on the Mt/cGNS mixing ratio to achieve the maximum at the ratio of 3/1. Rho 0 cells of a Mt function-deficient line were prepared to evaluate the enhancement of Mt membrane potential of rho 0 cells after the internalization of Mt-cGNS. When evaluated by using tetramethylrhodamine methyl ester reagent, the mitochondrial membrane potential of rho 0 cells after incubation with Mt-cGNS enhanced compared with that incubated with Mt only and maintained at a significantly higher level even for 6 days. The Mt-cGNS were internalized into rho 0 cells by an actin-dependent pathway, followed by fused with endogenous Mt. It is concluded that association with the cGNS enabled Mt to enhance the cellular internalization, followed by the fusion with endogenous Mt to maintain an enhanced Mt membrane potential.
Impact Statement
This study proposes an isolated mitochondria (Mt) delivery system to rescue the mitochondrial function. The cationized gelatin nanospheres association improved the internalization efficiency of exogenous mitochondria and therefore enhanced the mitochondrial activity. The exogenous Mt can fuse into the Mt original network, and the enhanced mitochondrial membrane potential can be maintained over 6 days. This system is promising to enhance the Mt therapeutic efficacy.
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