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).