Summary
The metabolic capacity of the eukaryotic cell to convert free energy contained in nutrients into ATP is a process accomplished by a multi-step system: the mitochondrial respiratory chain. This chain involves a series of electron-transferring enzymes and redox co-factors, whose biochemical characterization is the collective result of more than 50 years of scientists’ endeavors. The current knowledge describes in detail the structure and function of the individual proton-translocating “core” complexes of the respiratory chain (Complex I, III, IV). However, a holistic approach to the study of electrons transport from NAD-dependent substrates to oxygen has recently directed our attention to the existence of specific albeit dynamic interactions between the respiratory complexes. In this context, the respiratory complexes are envisaged to be either in form of highly ordered assemblies (i.e. supercomplexes) or as individual enzymes randomly distributed in the mitochondrial membrane. Either model of organization has functional consequences, which can be discussed in terms of the structural stability of the protein complexes and the kinetic efficiency of inter-complex electron transfer. Available experimental evidence suggests that Complex I and Complex III behave as assembled supercomplexes (ubiquinone-channeling) or as individual enzymes (ubiquinone-pool), depending on the lipid environment of the membrane. On the contrary, a strict association of Complexes III and Complex IV is not required for electron transfer via cytochrome c, although there are supercomplexes in bovine heart mitochondria, known as the respirasomes, that also include some molecules of Complex IV. Our recent experimental results demonstrate that the disruption of the supercomplex I1–III2 enhances the propensity of Complex I to generate the superoxide anion; we propose that any primary source of oxidative stress in mitochondria may perpetuate generation of reactive oxygen species by a vicious cycle involving supercomplex dissociation as a major determinant.
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Abbreviations
- BN-PAGE:
-
– Blue native polyacrylamide gel electrophoresis;
- CI–IV :
-
– Metabolic flux control coefficient of the corresponding respiratory complex;
- CoQ:
-
– Coenzyme Q ubiquinone;
- EPR:
-
– Electron paramagnetic resonance;
- ETF:
-
– Electron transfer flavoprotein;
- FP:
-
– Flavoprotein;
- O2 −·:
-
– Superoxide anion;
- OXPHOS:
-
– Oxidative phosphorylation system;
- PL:
-
– Phospholipids;
- ROS:
-
– Reactive oxygen species;
- SDS:
-
– Sodium dodecyl sulfate
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Acknowledgements
I would like to express my gratitude to my scientific mentor, Professor Giorgio Lenaz (University of Bologna, Italy), to whom I am indebted for the critical review of my work. I am also sincerely grateful to him for his valued example of attitude in science and for the generous helpful advices and stimulating ideas that he has shared with me during all these years.
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Genova, M.L. (2014). Electron Transport in the Mitochondrial Respiratory Chain. In: Hohmann-Marriott, M. (eds) The Structural Basis of Biological Energy Generation. Advances in Photosynthesis and Respiration, vol 39. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8742-0_21
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