title: COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation.
abstract: Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pérez-Pérez
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lobo-Jarne
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Dusanka
authors.initials: D
authors.lastname: Milenkovic
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Bratic
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: García-Bartolomé
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, CB2 0XY Cambridge, UK.
authors.forename: Erika
authors.initials: E
authors.lastname: Fernández-Vizarra
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM) and Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain; Instituto de Investigación Sanitaria Princesa (IIS-IP), 28006 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Cadenas
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Aitor
authors.initials: A
authors.lastname: Delmiro
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: García-Consuegra
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
authors.affiliation: Instituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, Spain. Electronic address: cugalde@h12o.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ugalde
mesh_terms: D000818:Animals; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010085:Oxidative Phosphorylation; D011485:Protein Binding; D055550:Protein Stability
chemical_list: D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III