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2017 ; 7
(1
): 10710
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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
#MMPMID28878349
Chang JC
; Hoel F
; Liu KH
; Wei YH
; Cheng FC
; Kuo SJ
; Tronstad KJ
; Liu CS
Sci Rep
2017[Sep]; 7
(1
): 10710
PMID28878349
show ga
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.