Fig. 4. Electrical circuit model reveals decreased mitochondrial ATP synthesis in early mitosis.

a, b Electrical circuit model of mitochondria, where ∆Ψm is the voltage across the circuit (a). The key components controlling ∆Ψm (ETC, ATP synthase, and leakage), all have their respective resistances (R_ETC, R_ATP, and R_Leak), which together form the total resistance (R) in the circuit (b). Oligomycin increases the R_ATP value to infinity. The difference in R values between control and oligomycin-treated cells reflects the R_ATP value. c Model fit to a typical L1210 single-cell TMRE data. TMRE signals were converted to approximate voltages and CDK1_on (light blue) and CDK1_off (dark blue) regions were fitted separately to derive the time constant (RC) values for each state. d Time constant (RC) values for CDK1_on (light blue) and CDK1_off (dark blue) regions in control and 1 µM oligomycin-treated L1210 cells. Data depict the mean (small square), median (horizontal bar), interquartile range (IQR) (box), and 1.5× IQR (whiskers). Statistical significance was assessed using one-way ANOVA followed by Sidakholm test. N denotes the number of independent experiments, n denotes the number of cells. e ATP synthesis rate (I_ATP) for 85 separate L1210 cells around cell division. Individual cells are drawn with thin opaque lines; the population average is drawn with a thick solid line. The colored areas reflect total amounts of ATP synthesized during early mitosis (red) and anaphase (light yellow). f Quantifications of relative ATP synthesis rates (I_ATP) in G2 (dark blue) and mitosis (light blue) as modeled on a single-cell level in non-arrested cells. G2 rates were obtained using RC values for CDK1 off, and the ∆Ψm observed prior to mitotic entry. Unpaired, two-tailed Student’s t test was used for statistical analysis. g Quantifications of the total ATP synthesized by mitochondria during early mitosis (from G2/M to M/A transition, red) and during anaphase (light yellow), when compared to a null-hypothesis where ATP synthesis rate remains at G2 levels throughout mitosis (dashed horizontal line). For panels (f, g), data depict mean ± SEM (see Supplementary Note 8 for error analysis), and the data are the same as in panel (d).