Abstract
Mitochondria in early embryonic hearts are not thought to produce ATP, yet they do produce reactive oxygen species (ROS) that regulate myocyte differentiation. To assess changes in ATP and ROS generation in the developing heart, we measured mitochondrial oxygen consumption, the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC), ETC supercomplex assembly, and ROS in embryonic mouse hearts. At embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the ETC complexes are present. We show that Cx-1 is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx −1, −3, and −4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In contrast, generation of reactive oxygen species (ROS), as measured with Amplex Red, is high at E9.5 and drops significantly by E11.5, coinciding with activation of the ETC. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in a decrease of ROS generation and an increase in OXPHOS due to the activation of Cx-1 and the formation of supercomplexes.
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