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

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 tra...

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Autores principales: Chang, Jui-Chih, Hoel, Fredrik, Liu, Ko-Hung, Wei, Yau-Huei, Cheng, Fu-Chou, Kuo, Shou-Jen, Tronstad, Karl Johan, Liu, Chin-San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587702/
https://www.ncbi.nlm.nih.gov/pubmed/28878349
http://dx.doi.org/10.1038/s41598-017-10870-5
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author Chang, Jui-Chih
Hoel, Fredrik
Liu, Ko-Hung
Wei, Yau-Huei
Cheng, Fu-Chou
Kuo, Shou-Jen
Tronstad, Karl Johan
Liu, Chin-San
author_facet Chang, Jui-Chih
Hoel, Fredrik
Liu, Ko-Hung
Wei, Yau-Huei
Cheng, Fu-Chou
Kuo, Shou-Jen
Tronstad, Karl Johan
Liu, Chin-San
author_sort Chang, Jui-Chih
collection PubMed
description 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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spelling pubmed-55877022017-09-13 Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation Chang, Jui-Chih Hoel, Fredrik Liu, Ko-Hung Wei, Yau-Huei Cheng, Fu-Chou Kuo, Shou-Jen Tronstad, Karl Johan Liu, Chin-San Sci Rep Article 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. Nature Publishing Group UK 2017-09-06 /pmc/articles/PMC5587702/ /pubmed/28878349 http://dx.doi.org/10.1038/s41598-017-10870-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chang, Jui-Chih
Hoel, Fredrik
Liu, Ko-Hung
Wei, Yau-Huei
Cheng, Fu-Chou
Kuo, Shou-Jen
Tronstad, Karl Johan
Liu, Chin-San
Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title_full Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title_fullStr Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title_full_unstemmed Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title_short Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation
title_sort peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the melas a3243g mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587702/
https://www.ncbi.nlm.nih.gov/pubmed/28878349
http://dx.doi.org/10.1038/s41598-017-10870-5
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