Functional role of mitochondrial respiratory supercomplexes.
Recent experimental evidence has replaced the random diffusion model of electron transfer with a model of supramolecular organisation based upon specific interactions between individual respiratory complexes. These supercomplexes were found to be functionally relevant by flux control analysis and to confer a kinetic advantage to NAD-linked respiration (channelling). However, the Coenzyme Q pool is still required for FAD-linked oxidations and for the proper equilibrium with Coenzyme Q bound in the supercomplex. Channelling in the cytochrome c region probably also occurs but does not seem to confer a particular kinetic advantage. The supramolecular association of individual complexes strongly depends on membrane lipid amount and composition and is affected by lipid peroxidation; it also seems to be modulated by membrane potential and protein phosphorylation. Additional properties of supercomplexes are stabilisation of Complex I, as evidenced by the destabilising effect on Complex I of mutations in either Complex III or IV, and prevention of excessive generation of reactive oxygen species. The dynamic character of the supercomplexes allows their involvement in metabolic adaptations and in control of cellular signalling pathways. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.
Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum-Università di Bologna, Via Irnerio 48, 40126 Bologna, Italy. Electronic address: marialuisa.genova@unibo.it.
Maria Luisa
ML
Genova
Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum-Università di Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Giorgio
G
Lenaz
D019069:Cell Respiration; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D014451:Ubiquinone / Q000378:metabolism
D008563:Membrane Lipids; D009097:Multienzyme Complexes; D014451:Ubiquinone
Cell signaling; Electron transfer; Mitochondria; Reactive oxygen species; Respiratory chain; Supercomplexes