Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts

Figure 5

Mitochondrial transfer by WJMSCs contributes to remodel mitochondrial morphology and rescue mitochondrial bioenergetics. (a) Representative image of mitochondrial morphology. Mitochondrial morphology was visualized by transfecting Cox4-DsRed. White rectangle represents highlighted segment enlarged in lower panel. (b, c) The MicroP algorithm categorized mitochondrial morphology into five types: small globe (blue), simple tube (green), twisted tube (orange), donut (red), and branching tube (purple). -400 mitochondria from 15-30 cells and three independent experiments. (c) Quantitative score of mitochondrial morphology. (d) OXPHOS-linked ATP production was dissected with the addition of ATPase inhibitor oligomycin. (e) OCR analysis. Vertical lines indicate the subsequent addition of the ATPase inhibitor oligomycin, the uncoupling reagent FCCP, and the inhibitors of the electron transport chain rotenone/antimycin A (Rot/AA). (f–i) Histograms individually representing basal (basal OCR), oligomycin-sensitive (ATP-linked OCR), FCCP-stimulated (maximal OCR), and the difference basal and maximal respiration (spare OCR). NS: no significance between the indicated groups. significantly different when compared to the indicated group. significantly different compared to any other DMSO-treated group. Con: control fibroblast from normal human; MF^Neg: MELAS fibroblast clone harboring negative mutation burden; MF^Hi: MELAS fibroblast clone harboring high mutation burden; OCR: oxygen consumption rate; ECAR: extracellular acidification rate.

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