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Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells


Hung, SSC and Van Bergen, NJ and Jackson, S and Liang, H and Mackey, DA and Hernandez, D and Lim, SY and Hewitt, AW and Trounce, I and Pebay, A and Wong, RCB, Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells, Aging, 8, (5) pp. 1-13. ISSN 1945-4589 (2016) [Refereed Article]


Copyright Statement

Copyright: Hung et al. Licensed under Creative Commons Attribution.

DOI: doi:10.18632/aging.100950


Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber's hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology.

Item Details

Item Type:Refereed Article
Keywords:cellular reprogramming, mitochondria, oxidative phosphorylation, induced pluripotent stem cells, Leberís hereditary optic neuropathy
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:108920
Year Published:2016
Web of Science® Times Cited:27
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-05-11
Last Modified:2022-08-26
Downloads:158 View Download Statistics

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