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Sci Rep. 2017 Sep 6;7(1):10710. doi: 10.1038/s41598-017-10870-5.

Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation.

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Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.
Department of Biomedicine, University of Bergen, Bergen, Norway.
Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Department of Medicine, Mackay Medical College, Taipei, Taiwan.
Stem Cell Center, Department of Medical Research, Taichung Veterans General Hospital, Changhua, Taiwan.
Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.
Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.


The cell penetrating peptide, Pep-1, has been shown to facilitate cellular uptake of foreign mitochondria but further research is required to evaluate the use of Pep-1-mediated mitochondrial delivery (PMD) in treating mitochondrial defects. Presently, we sought to determine whether mitochondrial transplantation rescue mitochondrial function in a cybrid cell model of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) disease. Following PMD, recipient cells had internalized donor mitochondria after 1 h, and expressed higher levels of normal mitochondrial DNA, particularly at the end of the treatment and 11 days later. After 4 days, mitochondrial respiratory function had recovered and biogenesis was evident in the Pep-1 and PMD groups, compared to the untreated MELAS group. However, only PMD was able to reverse the fusion-to-fission ratio of mitochondrial morphology, and mitochondria shaping proteins resembled the normal pattern seen in the control group. Cell survival following hydrogen peroxide-induced oxidative stress was also improved in the PMD group. Finally, we observed that PMD partially normalized cytokine expression, including that of interleukin (IL)-7, granulocyte macrophage-colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF), in the MELAS cells. Presently, our data further confirm the protective effects of PMD as well in MELAS disease.

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