Sidedness of inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by ethidium bromide

Higuti, Tomihiko; Yokota, Makoto; Arakaki, Naokatu; Hattori, Atsumi; Tani, Isamu

doi:10.1016/0005-2728(78)90183-4

Cited by 34 publications

(10 citation statements)

References 34 publications

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“…Other reports (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) have described proton movements in restricted domains or in isolated open membrane sheets not capable of sustaining a transmembrane pH gradient (which nevertheless can be energized, ostensibly by generation of an electrochemical H+ gradient for ATP synthesis) or have demonstrated that the pH may not account for the activities attributed to membrane "energization." Taken together, the observations suggest that there may be specific proton-conducting pathways in or on such energy-transducing membranes that allow them to carry out energy transduction without necessarily involving a pH gradient across the membrane.…”

mentioning

confidence: 99%

Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis.

Haines¹

1983

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

217

167

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Evidence has been gathering from several laboratories that protons in proton-pumping membranes move along or within the bilayer rather than exchange with the bulk phase. These experiments are typically conducted on the natural membrane in vivo or in vitro or on fragments of natural membrane. Anionic lipids are present in all proton-pumping membranes. Model studies on the protonation state of the fatty acids of liposomes containing entrapped water show that the bilayers always contain mixtures of protonated and deprotonated carboxylates. Protonated fatty acids form stable acid-anion pairs with deprotonatedfatty acids through unusually strong hydrogen bonds. Such acid-anion dimers have a single negative charge, which is shared by the four negative oxygens of both headgroups. The two pK values of the resulting dimer will be significantly different from the pK of the monomeric species, so that the dimer will be stable over a wide pH range. It is proposed that anionic lipid headgroups in biological membranes share protons as acid-anion dimers and that anionic lipids thus trap and conduct protons along the headgroup domain of bilayers that contain such anionic lipids-. Protons pumped from the other side ofthe membrane may enter and move within the headgroup sheet because the protonation rate of negatively charged proton acceptors is 5 orders of magnitude faster than that of water. Protons trapped in the acidic headgroup sheet need not leave this region in order to be utilized by a responsive proton-translocating pore (a transport protein using the proton gradient). Experiments suggest the proton concentration in the headgroup domain may vary widely and the anionic lipid headgroup sheet may therefore function as a proton buffer. -Due to the Gouy-Chapman-Stern layer at polyanionic surfaces, anionic lipids will also sequester protons from the bulk solution at low and moderate ionic strengths. At high ionic strength metal cations may replace protons sequestered near the headgroups, but these cations cannot substitute for protons in the "proton-conducting pathway," which is based on hydrogen bonding.Recent experiments in several laboratories have suggested that protons that are translocated by proton-pumping membranes, such as those of mitochondria and halobacteria, need not enter the external bulk water phase in order to be utilized by protontransporting proteins ofthe membrane, such as ATP synthetase. Notable among these experiments are -those of Michel and Oesterhelt (1), who made careful measurements of proton-dependent ATP synthesis and pH changes in and near illuminated, Halobacterium halobium cells. They found, that the pH is not lowered in the bulk aqueous phase as the protons pumped.by the purple patches of bacteriorhodopsin are utilized by ATP synthetase, which is not present in the purple patches but is found at some distance in red patches ofthe same plasma membrane. They concluded that.the protons do not pass through the bulk aqueous phase but move very close to the membrane surface. This system is un...

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mentioning

confidence: 99%

Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis.

Haines¹

1983

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

217

167

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“…These results confirm that ADR -induced lipid peroxidation is partially due to a disturbance of the enzymatic detoxification of lipid peroxide. In a separate paper (Moon, 1982) using an anisotropic inhibitor of ethidium bromide (Higuti, 1978), it was demonstrated that the disturbance of negative charge formation at the inner membrane of mitochondria was greater in heart mitochondria, than in mitochondria of the liver and kidney. The results of the present paper, indicate that heart mitochondria are quite susceptible to ADR.…”

Section: Discussionmentioning

confidence: 99%

Effect of adriamycin on lipid peroxide, glutathione peroxidase and respiratory responses of mitochondria from the heart, liver and kidney.

et al. 1983

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“…15,16) All components of the medium used were essential to obtain a good respiratory index. Respiratory activities were measured with glutamate (10 mM) plus malate (5 mM) or succinate (10 mM) as substrates, and respiration at state 3 and state 4 was measured after the addition of ADP for a final concentration of 250 mM.…”

Section: Measurement Of Oxygen Consumptionmentioning

confidence: 99%

Functional Disorders of the Oxidative Phosphorylation System in the Heart Mitochondria of Mice with Juvenile Visceral Steatosis.

Suenaga

Arakaki

Morokami

et al. 2003

Biological & Pharmaceutical Bulletin

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Sidedness of inhibition of energy transduction in oxidative phosphorylation in rat liver mitochondria by ethidium bromide

Cited by 34 publications

References 34 publications

Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis.

Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis.

Effect of adriamycin on lipid peroxide, glutathione peroxidase and respiratory responses of mitochondria from the heart, liver and kidney.

Functional Disorders of the Oxidative Phosphorylation System in the Heart Mitochondria of Mice with Juvenile Visceral Steatosis.

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