Rapid release of Mg2+ from liver mitochondria by nonesterified long-chain fatty acids in alkaline media

The effect of surface-potential modulators on palmitate/Ca2+-induced formation of lipid pores was studied in liposomal and inner mitochondrial membranes. Pore formation was monitored by sulforhodamine B release from liposomes and swelling of mitochondria. ζ-potential in liposomes was determined from electrophoretic mobility. Replacement of sucrose as the osmotic agent with KCl decreased negative ζ-potential in liposomes and increased resistance of both mitochondria and liposomes to the pore inducers, palmitic acid, and Ca2+. Micromolar Mg2+ also inhibited palmitate/Ca2+-induced permeabilization of liposomes. The rate of palmitate/Ca2+-induced, cyclosporin A-insensitive swelling of mitochondria increased 22% upon increasing pH from 7.0 to 7.8. At below the critical micelle concentration, the cationic detergent cetyltrimethylammonium bromide (10 μM) and the anionic surfactant sodium dodecylsulfate (10–50 μM) made the ζ-potential less and more negative, respectively, and inhibited and stimulated opening of mitochondrial palmitate/Ca2+-induced lipid pores. Taken together, the findings indicate that surface potential regulates palmitate/Ca2+-induced lipid pore opening.

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“…2). At 8.0 and above, palmitic acid alone induced mitochondrial swelling, consistent with previous reports [32, 33]. …”

Section: Resultssupporting

confidence: 92%

“…K + , Mg 2+ , and other cations also regulate mitochondrial permeabilization by inhibiting the MPT pore opening [28, 37, 38]. In K + -containing alkaline medium, fatty acids themselves induce nonspecific swelling of mitochondria that is not related to opening of MPT pores [32, 33, 39]. …”

Section: Discussionmentioning

confidence: 99%

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Belosludtsev

Belosludtseva

Агафонов

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Although there is some variability in reported efficacy of laurate (C12) depending on the parameter assessed, substantially lower efficacy for both laurate and stearate compared with myristate and palmitate as found in the tubules (Fig. 2) has been commonly described (18,56,74). Cis-unsaturation decreases the distance between the two ends of the molecule and confers substantial additional protonophoric activity (e.g., linoleate and oleate vs. stearate, and arachidonate vs. arachidic acid in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of long-chain NEFA to flip-flop across the membrane in their protonated form and, therefore, their protonophoric activity depend on the presence of an unsubstituted carboxylic acid and absence of changes to the hydrocarbon chain that alter its hydrophobicity (38,74). For saturated NEFA, it is consistently maximal at chain lengths of 14 (myristate) and 16 (palmitate) as assessed by a variety of different end points reflecting NEFA entry into the matrix (5,18,45,51,56,74,80). Although there is some variability in reported efficacy of laurate (C12) depending on the parameter assessed, substantially lower efficacy for both laurate and stearate compared with myristate and palmitate as found in the tubules (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Cis-unsaturation decreases the distance between the two ends of the molecule and confers substantial additional protonophoric activity (e.g., linoleate and oleate vs. stearate, and arachidonate vs. arachidic acid in Fig. 2) (5,18,45,51,56,61,74,80). The transbilayer mobility of undissociated NEFA is greatest when the hydrodynamic length of the molecule is close to half the thickness of the hydrodynamic core of the membrane (38,72).…”

Section: Discussionmentioning

confidence: 99%

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Alleviation of fatty acid and hypoxia-reoxygenation-induced proximal tubule deenergization by ADP/ATP carrier inhibition and glutamate

Feldkamp

Kribben

Roeser

et al. 2007

American Journal of Physiology-Renal Physiology

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Kidney proximal tubules develop a severe but highly reversible energetic deficit due to nonesterified fatty acid (NEFA)-induced dissipation of mitochondrial membrane potential (DeltaPsi(m)) during reoxygenation after severe hypoxia. To assess the mechanism for this behavior, we have compared the efficacies of different NEFA for inducing mitochondrial deenergization in permeabilized tubules measured using safranin O uptake and studied the modification of NEFA-induced deenergization by inhibitors of the ADP/ATP carrier and glutamate using both normoxic tubules treated with exogenous NEFA and tubules deenergized during hypoxia-reoxygenation (H/R). Among the long-chain NEFA that accumulate during H/R of isolated tubules and ischemia-reperfusion of the kidney in vivo, oleate, linoleate, and arachidonate had strong effects to dissipate DeltaPsi(m) that were slightly greater than palmitate, while stearate was inactive at concentrations reached in the cells. This behavior correlates well with the protonophoric effects of each NEFA. Inhibition of the ADP/ATP carrier with either carboxyatractyloside or bongkrekic acid or addition of glutamate to compete for the aspartate/glutamate carrier improved DeltaPsi(m) in the presence of exogenous oleate and after H/R. Effects on the two carriers were additive and restored safranin O uptake to as much as 80% of normal under both conditions. The data strongly support NEFA cycling across the inner mitochondrial membrane using anion carriers as the main mechanism for NEFA-induced deenergization in this system and provide the first evidence for a contribution of this process to pathophysiological events that impact importantly on energetics of intact cells.

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Magnesium Extravaganza: A Critical Compendium of Current Research into Cellular Mg2+ Transporters Other than TRPM6/7

Kolísek

Sponder

Pilchová

et al. 2018

Reviews of Physiology, Biochemistry and Pharmacology

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Rapid release of Mg2+ from liver mitochondria by nonesterified long-chain fatty acids in alkaline media

Cited by 14 publications

References 41 publications

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Effect of surface-potential modulators on the opening of lipid pores in liposomal and mitochondrial inner membranes induced by palmitate and calcium ions

Alleviation of fatty acid and hypoxia-reoxygenation-induced proximal tubule deenergization by ADP/ATP carrier inhibition and glutamate

Magnesium Extravaganza: A Critical Compendium of Current Research into Cellular Mg2+ Transporters Other than TRPM6/7

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