Extended Data Fig. 8: Reduced oxygen consumption coordinated with electro-mitochondrial decoupling.
From: Electro-metabolic coupling in multi-chambered vascularized human cardiac organoids
a, Representative kinetic measurements of interstitial oxygen content and mean oxygen content analysis in non-homogenous MCUKO or Non-targeting sgRNA cardiac organoids. Analysis shows a decrease in oscillation amplitude and an increase in oscillation frequency in the MCUKO organoids, coupled with an increase in mean oxygen content (n = 3, p < 0.001). Mean of 3 biological replicates; error bars,s.e.m. Significance was determined using two tailed t-test. Cardiac organoid graphs were taken from Fig. 6c. b, Representative kinetic measurements of interstitial oxygen content and mean oxygen content analysis in cardiac organoids treated with DMSO (Control), 10 μM mitoxantrone (Mitoxantrone) or 10 μM mitoxantrone, and 100 μM AMP-activated protein kinase (AMPK) activator metformin (Mitoxantrone + Metformin). Analysis shows a decrease in oscillation amplitude and an increase in oscillation frequency in the mitoxantrone-treated organoids, coupled with an increase in mean oxygen content (n = 3, p < 0.001). Metformin reverts these changes, restoring mean oxygen content to levels not significantly different than the control (n = 3, p > 0.05). Cardiac organoid graphs were taken from Fig. 6e. Mean of 3 biological replicates; error bars,s.e.m. Significance was determined using two tailed t-test. c, Representative kinetic measurements of interstitial oxygen content and mean oxygen content analysis in porcine cardiac tissue exposed to DMSO (control), 10 μM of blebbistatin, 10 µM mitoxantrone, or 10 µM mitoxantrone, and 100 μM metformin (mitoxantrone + metformin). Analysis shows that blebbistatin does not change oscillation amplitude and oscillation frequency or mean oxygen content (n = 3, p > 0.05). Mitoxantrone-treated organoids show a decrease in oscillation amplitude and an increase in oscillation frequency, coupled with an increase in mean oxygen content (n = 3, p < 0.001). Metformin partly reverts these changes, increasing mean oxygen content by 29% (n = 3, p < 0.001). Porcine cardiac tissue graphs were taken from Fig. 8d. Mean of 3 biological replicates; error bars,s.e.m. Significance was determined using one-way ANOVA with Dunnett multiple comparison correction.
