Evidence of the Proximity of ATP Synthase Subunits 6 (a) in the Inner Mitochondrial Membrane and in the Supramolecular Forms of Saccharomyces cerevisiae ATP Synthase

Velours, Jean; Stinès-Chaumeil, Claire; Habersetzer, Johan; Chaignepain, Stéphane; Dautant, Alain; Brèthes, Daniel

doi:10.1074/jbc.m111.275776

Cited by 21 publications

(16 citation statements)

References 53 publications

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“…However, the secondary structure of the N-terminus of subunit a (containing Cys23) suggests that it may be flexible and thus allow convergence within the minimal distance required for disulfide bond formation. This would be consistent with the observation that Cu 2+ -induced a-a dimers form at room temperature but not on ice [45]. In keeping with these findings, a Δe strain carrying a homoplasmic C23S mutation on subunit a no longer formed dimers after treatment with Cu 2+ even at low detergent concentrations (Fig.…”

Section: +supporting

confidence: 90%

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High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits

Carraro

Checchetto

Sartori

et al. 2018

Cell Physiol Biochem

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Background/Aims: The permeability transition pore (PTP) is an unselective, Ca²⁺-dependent high conductance channel of the inner mitochondrial membrane whose molecular identity has long remained a mystery. The most recent hypothesis is that pore formation involves the F-ATP synthase, which consistently generates Ca²⁺-activated channels. Available structures do not display obvious features that can accommodate a channel; thus, how the pore can form and whether its activity can be entirely assigned to F-ATP synthase is the matter of debate. In this study, we investigated the role of F-ATP synthase subunits e, g and b in PTP formation. Methods: Yeast null mutants for e, g and the first transmembrane (TM) α-helix of subunit b were generated and evaluated for mitochondrial morphology (electron microscopy), membrane potential (Rhodamine123 fluorescence) and respiration (Clark electrode). Homoplasmic C23S mutant of subunit a was generated by in vitro mutagenesis followed by biolistic transformation. F-ATP synthase assembly was evaluated by BN-PAGE analysis. Cu²⁺ treatment was used to induce the formation of F-ATP synthase dimers in the absence of e and g subunits. The electrophysiological properties of F-ATP synthase were assessed in planar lipid bilayers. Results: Null mutants for the subunits e and g display dimer formation upon Cu²⁺ treatment and show PTP-dependent mitochondrial Ca²⁺ release but not swelling. Cu²⁺ treatment causes formation of disulfide bridges between Cys23 of subunits a that stabilize dimers in absence of e and g subunits and favors the open state of wild-type F-ATP synthase channels. Absence of e and g subunits decreases conductance of the F-ATP synthase channel about tenfold. Ablation of the first TM of subunit b, which creates a distinct lateral domain with e and g, further affected channel activity. Conclusion: F-ATP synthase e, g and b subunits create a domain within the membrane that is critical for the generation of the high-conductance channel, thus is a prime candidate for PTP formation. Subunits e and g are only present in eukaryotes and may have evolved to confer this novel function to F-ATP synthase.

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Section: +supporting

confidence: 90%

“…Cu 2+ has been widely used to investigate thiol-mediated protein-protein interactions and organization of yeast F-ATP synthase. Biochemical studies suggested that homodimers form at subunit a via its unique Cys23 [45]. In the recent F o map, Cys23 residues of adjacent subunits face one another at an estimated distance of 22 Å (Fig.…”

Section: +mentioning

confidence: 95%

High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits

Carraro

Checchetto

Sartori

et al. 2018

Cell Physiol Biochem

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“…Consistent with this possibility, we did detect dimers in BN-PAGE after treatment with CuCl 2 (Fig. 4D), which promotes formation of disulfide bridges between adjacent cysteine residues of the monomers (45,47,48). Not all of the monomers dimerized after CuCl 2 treatment (Fig.…”

Section: Purified F-atp Synthase Dimers Possess Channel Activity-supporting

confidence: 78%

Channel Formation by Yeast F-ATP Synthase and the Role of Dimerization in the Mitochondrial Permeability Transition

Carraro

Giorgio

Šileikytė

et al. 2014

Journal of Biological Chemistry

145

128

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“…The fit places CypD close to regions of the peripheral stalk that are likely to contain the N-terminal part of subunit b (Fig. S2 A and B, magenta) (37,38), for which there is at present no X-ray structure. However, more recently, Giorgio et al reported that CypD interacts with the ATP synthase subunit OSCP (39), which is located on top of the F 1 head (Fig.…”

Section: Resultsmentioning

confidence: 93%

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

Daum

Walter

Horst

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

214

195

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Aging is one of the most fundamental, yet least understood biological processes that affect all forms of eukaryotic life. Mitochondria are intimately involved in aging, but the underlying molecular mechanisms are largely unknown. Electron cryotomography of whole mitochondria from the aging model organism Podospora anserina revealed profound age-dependent changes in membrane architecture. With increasing age, the typical cristae disappear and the inner membrane vesiculates. The ATP synthase dimers that form rows at the cristae tips dissociate into monomers in inner-membrane vesicles, and the membrane curvature at the ATP synthase inverts. Dissociation of the ATP synthase dimer may involve the peptidyl prolyl isomerase cyclophilin D. Finally, the outer membrane ruptures near large contact-site complexes, releasing apoptogens into the cytoplasm. Inner-membrane vesiculation and dissociation of ATP synthase dimers would impair the ability of mitochondria to supply the cell with sufficient ATP to maintain essential cellular functions.subtomogram averaging | cell death

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Evidence of the Proximity of ATP Synthase Subunits 6 (a) in the Inner Mitochondrial Membrane and in the Supramolecular Forms of Saccharomyces cerevisiae ATP Synthase

Cited by 21 publications

References 53 publications

High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits

High-Conductance Channel Formation in Yeast Mitochondria is Mediated by F-ATP Synthase e and g Subunits

Channel Formation by Yeast F-ATP Synthase and the Role of Dimerization in the Mitochondrial Permeability Transition

Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria

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