Szibor et al. (1) concluded that mitochondrial pyruvate oxidation is regulated primarily by cytosolic Ca2+ ([Ca2+]cyt) activation of the malate-aspartate shuttle, rather than by mitochondrial Ca2+ ([Ca2+]mit) activation of intramitochondrial dehydrogenases. Pyruvate dehydrogenase (PDH) activity largely reflects the ratio of active nonphosphorylated PDH to inactive phosphorylated PDH (PDHP) (2), but Szibor et al. (1) did not measure PDH/PDHP ratios. Moreover, their studies used unphysiological conditions with isolated mitochondria (saturating ADP); with synaptosomes, thymocytes, and fibroblasts (uncoupler and high pyruvate); and with perfused hearts (high pyruvate).