Mechanism of action of valinomycin on mitochondria

Moore, Charlotte E.; Pressman, Berton C.

doi:10.1016/0006-291x(64)90505-4

Cited by 494 publications

(153 citation statements)

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“…This has been tested making use of the antibiotic valinornycin which is known to increase the membrane conductivity selectively for K+, Cs+ and Rb+-ions [27]. The acceleration of the electric potential decay induced by low concentrations of valinomycin is depicted in Fig.4.…”

Section: Resultsmentioning

confidence: 99%

The Necessity of an Electric Potential Difference and its Use for Photophosphorylation in Short Flash Groups

Junge

Rumberg

Schröder

1970

European Journal of Biochemistry

166

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The ATP-synthesis and the electric phenomena on the thylakoid membrane have been studied under excitation of photosynthesis with short flash groups. The light induced electric potential difference has been measured by means of field indicating absorption changes around 623 nm.It is shown that upon excitation with short %ash groups a certain electric potential difference is required before ATP can be synthesized. Moreover it is confirmed that the ATP-synthesis is accompanied by an additional flux of protons down their electrochemical potential gradient. Correlation between the number of protons which have flowed across the ATPase coupled pathway, and the number of ATP-molecules which have been formed, yields a ratio H+/ATP = 3.Since this ratio includes only those protons, which have interacted with the ATPase complex, it represents the lower limit for H+/ATP-ratios determined by any other method.The necessity of a certain electric potential difference and the fact that 3 H+ have to be translocated down their electrochemical potential difference before one molecule of ATP can be synthesized is consistent with the chemiosmotic postulate, that the ADP N P bond energy is derived from the electrochemical potential difference of the proton across the coupling membrane.With respect to the alternative hypothesis for phosphorylation, the results impose grave restriction on a phosphorylation driven only by the free energy of a chemical intermediate, The main difference between this modSed chemical hypothesis and the chemiosmotic one lies in the possibility of a "direct squiggle phosphorylation" in the former one, while the latter predictsTthat phosphorylation occurs only with an intermediate electrochemical potential difference.I n this paper we question whether such a "direct squiggle phosphorylation" does exist, or if this cannot be answered conclusively, we shall try, to derive limiting properties for the as yet unspecified "direct squiggle phosphorylation". This paper will not be concerned with any squiggle which may operate in series with or cooperate in parallel with and necessarily linked to a chemiosmotic mechanism. Moreover it shall be completely ignored

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Section: Resultsmentioning

confidence: 99%

The Necessity of an Electric Potential Difference and its Use for Photophosphorylation in Short Flash Groups

Junge

Rumberg

Schröder

1970

European Journal of Biochemistry

166

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“…With animal mitochondria this equilibration does not effectively uncouple respiration unless an anion (e.g., phosphate or acetate) is present which can be transported at the expense of a proton gradient, in which case there is active swelling (19,20). If permeability to chloride is induced, respiration is released by ValP in active KCI extrusion (3).…”

Section: Introductionmentioning

confidence: 99%

The Action of Valinomycin in Uncoupling Corn Mitochondria

Hensley¹,

Hanson²

1975

Plant Physiol.

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ADP (9,13, 15,26). As in animal mitochondria (6), Val plus K+ will activate plant mitochondrial ATPase, being fully as effective as 2,4-dinitrophenol (12). To an impressive degree, Val plus K+ produces uncoupling of plant mitochondria resembling that obtained with the classical, proton-conducting uncouplers.Rat liver (18) and beef heart (4) mitochondria are believed to possess antiporters for exchanging Na+ for H+, with much less activity in K+/H+ exchange. It has been suggested (P. Mitchell, private communication) that the release of respiration in corn mitochondria with little swelling (9) could arise from the activity of a K+/H+ antiporter, and that such an antiporter may be characteristic of plants. It is characteristic of plants that Na+ is not an essential element (some halophytes excepted), and it is reasonable to speculate that an active K+/H+ antiporter exists.We report here an investigation of Val-uncoupled respiration of corn mitochondria as related to influx and efflux pumping of phosphate salts. (The term "pumping" is used to denote energy-linked salt transport in or out of the matrix.) It seems that a K+/H+ antiporter may in fact exist, but that it is not really K+ specific. Specificity seems to lie primarily with a lipid barrier which has high resistance to cation penetration unless ionophores are used. Uncouplers in turn may promote penetration of protons to this cation+/H+ antiporter.Valinomycin is widely used as a lipid-soluble, potassiumbinding ionophore for rapidly equilibrating the electrochemical potential of K+ across membranes. With animal mitochondria this equilibration does not effectively uncouple respiration unless an anion (e.g., phosphate or acetate) is present which can be transported at the expense of a proton gradient, in which case there is active swelling (19,20). If permeability to chloride is induced, respiration is released by ValP in active KCI extrusion (3). With low K+ concentrations, Val does not eliminate respiratory control or phosphorylation of liver mitochondria (11,17,21).Plant mitochondria are at least quantitatively different. There is rapid passive swelling in KCI at neutral pH which is accelerated by gramicidin D (15, 27) or Val (13,25), demonstrating permeability to chloride which is rate limited by accompanying cation influx. Efflux pumping of the KCI with concomitant shrinkage is not uncoupled by Val although respiration is accelerated (13). With sucrose or mannitol- MATERIALS AND METHODSCorn mitochondria (Zea mays L., WF9-Tms X M14) were isolated as previously described (8) in 0.4 M sucrose, 50 mM KH,PO, 5 mm EGTA, adjusted to pH 7.6 with tris. In certain cases endogenous K+ was reduced by substituting NaH,PO4 as buffer; this lowered the endogenous K+ from 172 to 78 nmoles/mg of protein. Potassium was determined by flame emission spectroscopy on 5% trichloroacetic acid extracts.Reactions were run in 4-ml volumes at 29 C with simultaneous recordings of 02 and per cent transmission as previously described (8, 9), except that full scale transmittance ...

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“…Pressman (7,8) showed that the stimulation of respiration by valinomycin required inorganic phosphate (Pi) and was associated with uptake of K + and extrusion of H + by mitochondria. R b + and Cs + could replace K + in the system, but Na + and Li + could not.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Valinomycin on Potassium and Sodium Permeability of HK and LK Sheep Red Cells

Tosteson

Cook

Andreoli

et al. 1967

The Journal of General Physiology

109

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A B S T R A C1 T A cyclic depsipeptide antibiotic, valinomycin, was found to produce increased selective permeability of the plasma membranes of H K and L K sheep red blood cells to potassium but not to sodium ions. The compound had relatively little effect on the active extrusion of sodium from H K sheep red blood cells or on the Na + K-stimulated ATPase activity of membranes derived from these cells. It is proposed that the selective cation permeability produced by this compound depends primarily on steric factors, particularly the relationship between the diameter of the ring and the effective diameter of the ion. The significance of these results for the problem of the mechanism of ionic selectivity in natural membranes is discussed. (4, 5) showed that this conclusion was erroneous and that n equals 3 in the naturally occurring antibiotic. It is n o t e w o r t h y that all a -a m i n o groups (of n-and L-valine residues) a n d s -h y d r o x y l groups (of L-lactate and D-hydroxyvalerate) in the molecule are involved in peptide or ester linkages respectively. T h e side chains of all residues consist entirely of one or m o r e methyl groups. This cyclic structure is shown clearly in the space-filling Corey-Pauling model of valinomycin, a p h o t o g r a p h of which is shown in Fig. 1.T h e effect of valinomycin on mitochondria was first studied by M c M u r r a y and Begg (6) who showed that the c o m p o u n d u n d e r certain circumstances ~5~3

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Mechanism of action of valinomycin on mitochondria

Cited by 494 publications

References 4 publications

The Necessity of an Electric Potential Difference and its Use for Photophosphorylation in Short Flash Groups

The Necessity of an Electric Potential Difference and its Use for Photophosphorylation in Short Flash Groups

The Action of Valinomycin in Uncoupling Corn Mitochondria

The Effect of Valinomycin on Potassium and Sodium Permeability of HK and LK Sheep Red Cells

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