For statistical analysis each patient cell line was tested against the average of the 3 control cell lines.
Indeed, a patient cell line with a low ROS level had a high redox sensitivity (P7), or opposite (P6).
Figure 3a shows that both KH176 and KH176m could protect patient cell line P4 from BSO-induced death in the Redox Stress Survival assay.
Interestingly, KH176(m) was also active in patient cell line P7 displaying a lower ROS level than healthy controls (Supplementary Table S1 and Fig. 1).
Although an increase in ROS level can lead to a redox imbalance, we noted that this correlation was not necessarily seen in all patient cell lines.
We have tried mitoSOX for mitochondrial superoxides detection but did not detect differences between control and patient cell lines (data not shown).
With treatment, this increased to 15.9% in control cells and to 28.8% in patient cell (Fig. 3g,h; Supplementary Fig. 5g,h), illustrating the dependence of CII substrates in the patient cells to reach normal respiratory function.
(a) Basal ROS levels in 3 healthy control cell lines (C1 to C3) and 7 patient cell lines (P1 to P7) bearing mutations in different nuclear encoded Complex I subunits.
Blanchet, L. & Buydens, M. C. Smeitink, J. a M., Willems, P. H. G. M. & Koopman, W. J. H. Isolated mitochondrial complex I deficiency: explorative data analysis of patient cell parameters.
Repairing the genetic mutation in the FMR1 gene in an FXS patient cell line restored fragile X mental retardation protein (FMRP) expression and fully rescued synaptic retinoic acid signaling.
In the case when patients carrying certain genetic mutations are not accessible, wild-type stem cells can also be introduced with genetic variants to create "patient" cell lines (Fig. 1A).
