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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.

Author information

1
Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.
2
Department of Biomedicine, University of Bergen, Bergen, Norway.
3
Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
4
Department of Medicine, Mackay Medical College, Taipei, Taiwan.
5
Stem Cell Center, Department of Medical Research, Taichung Veterans General Hospital, Changhua, Taiwan.
6
Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
7
Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan. 26602@cch.org.tw.
8
Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan. 26602@cch.org.tw.

Abstract

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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