Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?

Genova, Maria Luisa; Baracca, Alessandra; Biondi, A.; Casalena, Gabriella; Faccioli, Marco; Falasca, Anna Ida; Formiggini, Gabriella; Sgarbi, Gianluca; Lenaz, Giorgio

doi:10.1016/j.bbabio.2008.04.007

Cited by 112 publications

(87 citation statements)

References 60 publications

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“…We have previously demonstrated that lipid peroxidation can dissociate the supramolecular assemblies (27); thus, here we confirm our conclusion that primary causes of oxidative stress may perpetuate reactive oxygen species (ROS) generation by a vicious circle involving supercomplex dissociation as a major determinant. It is easy to foresee the implications of these findings in human diseases and in aging, where oxidative stress plays a major etiologic and pathogenic role.…”

Section: Innovationsupporting

confidence: 76%

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

Maranzana

Barbero

Falasca

et al. 2013

Antioxidants & Redox Signaling

345

265

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Aims: 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. Innovation: Dissociation of supercomplexes may link oxidative stress and energy failure in a vicious circle. Conclusion: 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.

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Section: Innovationsupporting

confidence: 76%

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

Maranzana

Barbero

Falasca

et al. 2013

Antioxidants & Redox Signaling

345

265

View full text Add to dashboard Cite

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“…Their association into megacomplexes was proposed to form a functional unit known as the "respirasome" (7,60,69). Because the electron transport chain is one of the major contributors to free radicals in the cell, respirasomes could minimize the generation of reactive oxygen species (ROS) by allowing a more efficient electron transfer and substrate channeling among the complexes, therefore avoiding the diffusion of reactive intermediates (29,42).…”

mentioning

confidence: 99%

Cells Lacking Rieske Iron-Sulfur Protein Have a Reactive Oxygen Species-Associated Decrease in Respiratory Complexes I and IV

Díaz

Enríquez

Moraes

2012

Molecular and Cellular Biology

113

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Mitochondrial respiratory complexes of the electron transport chain (CI, CIII, and CIV) can be assembled into larger structures forming supercomplexes. We analyzed the assembly/stability of respiratory complexes in mouse lung fibroblasts lacking the Rieske iron-sulfur protein (RISP knockout [KO]cells), one of the catalytic subunits of CIII. In the absence of RISP, most of the remaining CIII subunits were able to assemble into a large precomplex that lacked enzymatic activity. CI, CIV, and supercomplexes were decreased in the RISP-deficient cells. Reintroduction of RISP into KO cells restored CIII activity and increased the levels of active CI, CIV, and supercomplexes. We found that hypoxia (1% O 2 ) resulted in increased levels of CI, CIV, and supercomplex assembly in RISP KO cells. In addition, treatment of control cells with different oxidative phosphorylation (OXPHOS) inhibitors showed that compounds known to generate reactive oxygen species (ROS) (e.g., antimycin A and oligomycin) had a negative impact on CI and supercomplex levels. Accordingly, a superoxide dismutase (SOD) mimetic compound and SOD2 overexpression provided a partial increase in supercomplex levels in the RISP KO cells. Our data suggest that the stability of CI, CIV, and supercomplexes is regulated by ROS in the context of defective oxidative phosphorylation.

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“…A supramolecular assembly with NADH oxidase activity in the membranes of the bacterium Paracoccus denitrificans constitutes a complete respirasome and includes complexes I, III, and IV (17). Several roles for association between proteins of a respiratory pathway have been proposed in the literature, including substrate channeling, optimization of electron transfer, and protein stabilization (10).…”

mentioning

confidence: 99%

New Functional Sulfide Oxidase-Oxygen Reductase Supercomplex in the Membrane of the Hyperthermophilic Bacterium Aquifex aeolicus

Prunetti

Infossi

Brugna

et al. 2010

Journal of Biological Chemistry

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Aquifex aeolicus, a hyperthermophilic and microaerophilic bacterium, obtains energy for growth from inorganic compounds alone. It was previously proposed that one of the respiratory pathways in this organism consists of the electron transfer from hydrogen sulfide (H 2 S) to molecular oxygen. H 2 S is oxidized by the sulfide quinone reductase, a membrane-bound flavoenzyme, which reduces the quinone pool. We have purified and characterized a novel membrane-bound multienzyme supercomplex that brings together all the molecular components involved in this bioenergetic chain. Our results indicate that this purified structure consists of one dimeric bc 1 complex (complex III), one cytochrome c oxidase (complex IV), and one or two sulfide quinone reductases as well as traces of the monoheme cytochrome c 555 and quinone molecules. In addition, this work strongly suggests that the cytochrome c oxidase in the supercomplex is a ba 3 -type enzyme. The supercomplex has a molecular mass of about 350 kDa and is enzymatically functional, reducing O 2 in the presence of the electron donor, H 2 S. This is the first demonstration of the existence of such a respirasome carrying a sulfide oxidase-oxygen reductase activity. Moreover, the kinetic properties of the sulfide quinone reductase change slightly when integrated in the supercomplex, compared with the free enzyme. We previously purified a complete respirasome involved in hydrogen oxidation and sulfur reduction from Aquifex aeolicus. Thus, two different bioenergetic pathways (sulfur reduction and sulfur oxidation) are organized in this bacterium as supramolecular structures in the membrane. A model for the energetic sulfur metabolism of Aquifex aeolicus is proposed.

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Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?

Cited by 112 publications

References 60 publications

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

Cells Lacking Rieske Iron-Sulfur Protein Have a Reactive Oxygen Species-Associated Decrease in Respiratory Complexes I and IV

New Functional Sulfide Oxidase-Oxygen Reductase Supercomplex in the Membrane of the Hyperthermophilic Bacterium Aquifex aeolicus

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