title: Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes.
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.
authors.affiliation: University of Rochester Medical Center, Department of Pediatrics, Division of Cardiology, 601 Elmwood Ave., Box 631, Rochester, New York 14642, United States of America.
authors.forename: Gisela
authors.initials: G
authors.lastname: Beutner
authors.affiliation: Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Ave., Rochester, New York 14642, United States of America.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Eliseev
authors.affiliation: University of Rochester Medical Center, Department of Pediatrics, Division of Cardiology, 601 Elmwood Ave., Box 631, Rochester, New York 14642, United States of America.
authors.forename: George A
authors.initials: GA
authors.lastname: Porter
mesh_terms: D000367:Age Factors; D000818:Animals; D004579:Electron Transport / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D042963:Electron Transport Complex II / Q000235:genetics* / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000235:genetics* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D055503:Protein Multimerization
chemical_list: D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III