Abstract
Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC 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 summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes.
Highlights
The heart is the first functional organ in the vertebrate embryo
Electron transport chain activity increases during embryonic cardiac development We recently showed that mitochondrial structure in cardiac myocytes becomes more complex and the mitochondrial membrane potential (Dym) increases as the heart develops leading to a drop in mitochondrial-derived oxidative stress that enhanced myocyte differentiation [6]
The formation of respiratory supercomplexes To increase the efficiency of the electron transport chain (ETC) in some tissues including the heart, Cx-1 is thought to form ‘‘solid state’’ supercomplexes with Cx-3, Cx-4, ubiquinone, and cytochrome c [8,10,30] as our data suggests that the efficiency of electron transfer from Cx-1 to Cx-3 increased with embryonic age, we investigated whether assembly of respiratory supercomplexes increases during cardiac development
Summary
The heart is the first functional organ in the vertebrate embryo. In the mouse, the heart begins to beat at about embryonic day (E) 8.25, and cardiac formation is largely complete by E14, the end of the embryonic period [1]. It is worth noting that these ideas about bioenergetics during embryonic cardiac development are largely inferred from older studies that have not been validated using modern techniques. Many studies suggest that mitochondrial function is important for development. We recently showed that changes in bioenergetics control myocyte differentiation in the embryonic heart [6], and similar changes in mitochondrial function play a role in stem cell differentiation [7]. It remains unclear how and when during cardiac development mitochondria begin to perform their primary function of producing energy. PLoS ONE gar_pone.0113330.3d 8/11/14 12:05:15 The Charlesworth Group, Wakefield +44(0)1924 369598 - Rev 9.0.225/W (Oct 13 2006)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
