Pyruvate supply by the MAS controls cardiac power in the working rat heart ex vivo.
A, representative pressure response trace during isolated heart perfusion with substrates (glucose (Gluc) and pyruvate (Pyr)) and inhibitors (AOA and Cin) added as indicated. B, cardiac power under metabolic conditions as indicated. C, glycolytic rate under conditions as indicated. Note that there is a reverse relationship of cardiac power and glycolytic rates, depending on metabolic conditions. D, cardiac power in isolated rat hearts using pyruvate as substrate. Note that AOA-induced inhibition of MAS does not affect the use of pyruvate. All data are shown as mean ± S.E. (error bars) of n = 10 experiments. Horizontal bars, significant difference with p < 0.05 determined using two-way ANOVA with Tukey's multiple-comparison test for comparisons as indicated. E, graphical abstract summarizing Ca2+-controlled balance of cellular workload and mitochondrial OXPHOS. Cytosolic pyruvate generation allows OXPHOS activation to a great extent, depending on demand and organ, whereas the mitochondrial Ca2+ import through MCU is, under physiologic conditions, largely dispensable.