Genova 2018 MiP2018

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Maria Luisa Genova
Respiratory supercomplexes: evidence for separate though interconnected compartments of Coenzyme Q10 in mammalian mitochondria.

Link: MiP2018

Tioli G, Falasca AI, Lenaz G, Genova ML (2018)

Event: MiP2018

COST Action MitoEAGLE

Experimental evidence has ascertained that the major respiratory complexes involved in energy conservation in mitochondria (i.e. complexes I, III and IV) are assembled as stoichiometric supramolecular units (supercomplexes, SCs) based upon specific, though dynamic, interactions. Although SCs have been revealed and characterized in mitochondria from a variety of cell types and organisms, their functional role is less well defined and still open to discussion [1,2]. Our kinetic studies [3] in frozen and thawed bovine heart mitochondria and in reconstituted proteoliposomes favour the concept that electron transfer between Complex I and Complex III is mediated by channelling of electrons through Coenzyme Q10 (CoQ10) molecules bound to the SC I1III2, thus providing kinetic advantage, in contrast with the previously accepted hypothesis that the transfer of reducing equivalents from Complex I to Complex III occur via random diffusion of CoQ10 embedded in the inner mitochondrial membrane (pool behaviour). On the contrary, electron transfer from Complex II to Complex III and from Complex III to Complex IV seems to operate by random diffusion of intermediate substrates between the partner enzymes. In particular, our results show that NADH-cytochrome c and succinate-cytochrome c oxidoreductase activity are almost completely additive, as it is expected of two independent metabolic routes. Moreover, the rate obtained by simultaneous addition of NADH and succinate is much higher than the rate predicted for a single homogeneous CoQ10 pool. However, when the pressure by the reducing substrates increases due to strong inhibition of Complex III, or when detergents destabilize the SCs, CoQ10 molecules bound in the SC I1III2 may exchange with free CoQ10 molecules in the membrane, thus approaching the rates predicted for a single pool. A slow dissociation equilibrium of CoQ10 from SC I1III2, and the consequent accessibility of CoQ10 pool to the same SC, may be a device by which the size of the pool determines saturation of the binding site(s) in the SC and controls oxidation of NAD-linked substrates in physiological conditions, also providing a rationale for the beneficial effect of exogenous CoQ10 supplementation on mitochondrial bioenergetics. Furthermore, another property provided by the SC I1III2 assembly is the control of the production of reactive oxygen species by Complex I [4], which might be important in the regulation of signal transduction from mitochondria.


Bioblast editor: Plangger M, Kandolf G


Labels:


Organism: Bovines  Tissue;cell: Heart 

Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex 




Affiliations

Tioli G(1), Falasca AI(2), Lenaz G(1), Genova ML(1)

  1. Dept Biomedical Neuromotor Sciences, Alma Mater Studiorum, Univ Bologna
  2. Dept Food Drug, Univ Parma; Italy. - marialuisa.genova@unibo.it

References

  1. Lenaz G, Tioli G, Falasca AI, Genova ML (2017) Respiratory supercomplexes in mitochondria, in: Mechanisms of primary energy transduction in biology (Ed. M. Wikström) The royal society of chemistry, London (UK) 12:296-337.
  2. Fedor JG, Hirst J (2018) Mitochondrial supercomplexes do not enhance catalysis by quinone channeling. Cell Metab 28:1-7.
  3. Lenaz G, Tioli G, Falasca AI, Genova ML (2016) Complex I function in mitochondrial supercomplexes. Biochim Biophys Acta 1857:991-1000.
  4. Maranzana E, Barbero G, Falasca AI, Lenaz G, Genova ML (2013) Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid Redox Signal 19:1469-80.