Inhibition of the bovine-heart mitochondrial F1-ATPase by cationic dyes and amphipathic peptides

Bullough, David A.; Ceccarelli, Eduardo A.; Roise, David; Allison, William S.

doi:10.1016/s0005-2728(89)80346-9

Cited by 59 publications

(48 citation statements)

References 25 publications

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“…Third, given mounting evidence that acidic residue clusters can bind calcium specifically [27,33,34], several candidate calcium-binding sites are evident in the globally acidic (pI 4.8) Fl-~-subunit. Most notable is a highly conserved superficial loop of the Fl-~-subunit that contains the acidic sequence DELSEED, is known to bind cationic inhibitors, and is not mirrored in the basic (theoretical pI 8.8) Fl-c~-subunit [19,32,35]. Consistent with calcium binding to acidic residue clusters, the Fl-[~-subunit exhibited the same apparent affinity (Fig.…”

Section: Discussionmentioning

confidence: 75%

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

1996

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Mitochondrial ATP synthase is responsive to changes in cytosolic calcium concentration, but the regulatory mechanisms are unclear. Here we identified a major 52 kDa calciumbinding protein in rat enamel cells as the mitochondrial ATP synthase Fl-~subunit. The Fl-~-subunit behaved as a low affinity and moderate capacity calcium-binding protein during comparative 45Ca overlay analyses. Equivalent behavior was shown by the Fl-[I-subunit from rat liver mitochondria, but not by the homologous Fl-a-subunit, supporting the specificity of calcium binding. Evidence that the catalytic Fr~-subuuit binds calcium specifically introduces new mechanistic possibilities for regulating ATP synthase, and thereby coordinating ATP production with demand for ATP-fuelled calcium pump activity.

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Section: Discussionmentioning

confidence: 75%

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

1996

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“…In contrast, rhodamine 6G acts as an uncompetitive inhibitor of MF 1 and as a noncompetitive inhibitor for isolated and membrane-bound ATP synthase F 0 F 1 from yeast (433). Rhodamine B and rhodamine 123 are considered to bind F 1 at more than one binding sites, while rhodamine 6G at high concentrations is believed to bind at least two binding sites (52). The precise location of rhodamine 6G binding sites in the three-dimensional structure of F 1 has yet to be identified (143).…”

Section: Amphiphilic Cationic Dyesmentioning

confidence: 67%

“…Rosaniline and malachite green inhibit MF 1 in a parabolic mixed fashion, indicating at least two binding sites at high concentrations (52).…”

Section: Amphiphilic Cationic Dyesmentioning

confidence: 93%

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Hong

Pedersen

2008

Microbiol Mol Biol Rev

276

302

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SUMMARY ATP synthase, a double-motor enzyme, plays various roles in the cell, participating not only in ATP synthesis but in ATP hydrolysis-dependent processes and in the regulation of a proton gradient across some membrane-dependent systems. Recent studies of ATP synthase as a potential molecular target for the treatment of some human diseases have displayed promising results, and this enzyme is now emerging as an attractive molecular target for the development of new therapies for a variety of diseases. Significantly, ATP synthase, because of its complex structure, is inhibited by a number of different inhibitors and provides diverse possibilities in the development of new ATP synthase-directed agents. In this review, we classify over 250 natural and synthetic inhibitors of ATP synthase reported to date and present their inhibitory sites and their known or proposed modes of action. The rich source of ATP synthase inhibitors and their known or purported sites of action presented in this review should provide valuable insights into their applications as potential scaffolds for new therapeutics for human and animal diseases as well as for the discovery of new pesticides and herbicides to help protect the world's food supply. Finally, as ATP synthase is now known to consist of two unique nanomotors involved in making ATP from ADP and Pi, the information provided in this review may greatly assist those investigators entering the emerging field of nanotechnology.

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“…Therefore, in this study, we tested the effects of various lipophilic cations such as quinacrine mustard and dequalinium, which are known inhibitors of mitochondrial F~-ATPase [11,12], on V-ATPase purified from bovine adrenal chromaffin granules. We found that the V-ATPase was also sensitive to these F~-ATPase inhibitors, and studied the mechanism of the inhibition.…”

Section: Introductionmentioning

confidence: 99%

“…cations inhibited Fi-ATPase [11,12]. We investigated the effects of the lipophilic cations on V-ATPase purified from bovine chromaffin granules in comparison with their effects on bacterial F-ATPase.…”

mentioning

confidence: 99%

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H⁺‐ATPase and F₀F₁‐ATP synthase

1995

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Various lipophilic cations, such as quinacrine mustard and dequalinium, which are known to inhibit mitochondrial F~-ATPase, strongly inhibited vacuolar H+-ATPase purified from bovine adrenal chromaffin granules. Quinacrine mustard bound irreversibly to vacuolar H+-ATPase suhunit A, and the 11 5 kDa accessory polypeptide and dithiothreitol had no effect. The binding was competitively inhibited by chlorpromazine and quinacrine, and these compounds specifically reduced the amount of labeling of subunit A. Quinacrine mustard also prevented the binding of [a-32p]ATP to subunit A but had no effect on the binding of [3H]N-ethylmaleimide to either subunit A or the 115 kDa accessory polypeptide. These results suggest that the binding site of quinacrine mustard in subunit A is not related to the N-ethylmaleimide-binding site(s), which is important for activity.

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Inhibition of the bovine-heart mitochondrial F1-ATPase by cationic dyes and amphipathic peptides

Cited by 59 publications

References 25 publications

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H⁺‐ATPase and F₀F₁‐ATP synthase

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Inhibition of the bovine-heart mitochondrial F1-ATPase by cationic dyes and amphipathic peptides

Cited by 59 publications

References 25 publications

Mitochondrial ATP synthase F1‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F1‐β‐subunit is a calcium‐binding protein

ATP Synthase and the Actions of Inhibitors Utilized To Study Its Roles in Human Health, Disease, and Other Scientific Areas

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H+‐ATPase and F0F1‐ATP synthase

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Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Mitochondrial ATP synthase F₁‐β‐subunit is a calcium‐binding protein

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H⁺‐ATPase and F₀F₁‐ATP synthase