title: Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I.
abstract: OBJECTIVE
  The mitochondrial respiratory chain is recognized today to be arranged in supramolecular assemblies (supercomplexes). Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. In the present study, we have directly addressed this issue by testing the ROS generation by Complex I in two experimental systems in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio.
  
  
  RESULTS
  The results of our investigation provide experimental evidence that the production of ROS is strongly increased in either model, supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I.
  
  
  METHODS
  Dissociation of supercomplexes may link oxidative stress and energy failure in a vicious circle.
  
  
  CONCLUSIONS
  Our findings support a central role of mitochondrial supramolecular structure in the development of the aging process and in the etiology and pathogenesis of most major chronic diseases.
authors.affiliation: 1 Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum, Università di Bologna , Bologna, Italy .
authors.forename: Evelina
authors.initials: E
authors.lastname: Maranzana
authors.forename: Giovanna
authors.initials: G
authors.lastname: Barbero
authors.forename: Anna Ida
authors.initials: AI
authors.lastname: Falasca
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Genova
mesh_terms: D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I