3.5 In vitro testing results show the possible role of utilizing MitoRAISE in detecting individual’s mitochondrial conditions
To obtain clinical meaning from MitoRAISE data, PBMCs from healthy volunteers and cancer patients were obtained, and the six components of mitochondrial function (GM-induced and S-induced ATP synthesis capacity, rotenone and malonate sensitivity, total ATP contents, and mtDNA CN) were measured (Figures 3A-F). Healthy blood was obtained from both males and females, but breast cancer patients were all females. Interestingly, when compared to healthy females, breast cancer patients had significantly high GM-induced ATP synthesis capacity (p = 0.006) while significantly low mtDNA CN (p<0.001). When compared to healthy males, breast cancer patients had significantly lower sensitivity to malonate (p=0.04) and significantly lower mtDNA copy number (p=0.001). When comparing healthy male and female, females had significantly lower GM-induced and S-induced ATP synthesis capacity (p= 0.048 and p=0.019).
Interestingly, when analyzing the correlation between the six components of mitochondrial function measured through MitoRAISE and some clinical features, we found a moderate to high negative correlation between weight and ATP synthesis capacity and weight and inhibitor sensitivity in both healthy males and females (ρ = -0.2~-0.5) yet only a weak negative correlation in breast cancer patients (ρ =-0.08~-0.23). There was a positive correlation between mtDNA CN and ATP synthesis capacity and mtDNA CN and inhibitory substrate sensitivity in healthy females but a negative correlation in breast cancer patients (Figure 3H-J).