Effect of metal cations on the inhibition of adenine nucleotide translocation by acyl‐coa

Duszyński, Jerzy; Wojtczak, Lech

doi:10.1016/0014-5793(75)81044-1

Cited by 20 publications

(4 citation statements)

References 12 publications

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“…With excess exogenous ADP, the low-affinity binding sites became saturated in both types of mitochondria, producing equal protection. In vivo a high proportion of AdNs are complexed with Mg 2ϩ (Davidson and Halestrap, 1987), whereas the ANT binds and transports only free AdNs anions (Duszynski and Wojtczak, 1975;Kramer, 1980). Thus, the low concentrations of endogenous free AdNs may not saturate the low-affinity binding sites of the ANT in striatal mitochondria, predisposing them to Ca 2ϩ -induced damage in vivo.…”

Section: Discussionmentioning

confidence: 99%

Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition

et al. 2003

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Mitochondria were simultaneously isolated from striatum and cortex of adult rats and compared in functional assays for their sensitivity to calcium activation of the permeability transition. Striatal mitochondria showed an increased dose-dependent sensitivity to Ca2+ compared with cortical mitochondria, as measured by mitochondrial depolarization, swelling, Ca2+ uptake, reactive oxygen species production, and respiration. Ratios of ATP to ADP were lower in striatal mitochondria exposed to calcium despite equal amounts of ADP and ATP under respiring and nonrespiring conditions. The Ca2+-induced changes were inhibited by cyclosporin A or ADP. These responses are consistent with Ca2+ activation of both low and high permeability pathways constituting the mitochondrial permeability transition. In addition to the striatal supersensitivity to induction of the permeability transition, cyclosporin A inhibition was less potent in striatal mitochondria. Immunoblots indicated that striatal mitochondria contained more cyclophilin D than cortical mitochondria. Thus striatal mitochondria may be selectively vulnerable to the permeability transition. Subsequent mitochondrial dysfunction could contribute to the initial toxicity of striatal neurons in Huntington's disease.

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Section: Discussionmentioning

confidence: 99%

Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition

et al. 2003

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“…The inhibition is of a competitive character (Duszynski and Wojtczak, 1975) and strongly depends on the carbon chain length of the fatty acyl moiety (Morel et al, 1974). Further evidence that FAs, in their anionic form, can be substrates for transport by ANT was given by their inhibitory effect on ATP and ADP exchanges (Wojtczak and Zaluska, 1967; Schonfeld et al, 1996; Klingenberg, 2008).…”

Section: Fatty Acids and Mitochondrial Functionmentioning

confidence: 99%

Mitochondrial and cellular mechanisms for managing lipid excess

2014

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Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete. Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates. Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g., exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain reactive oxygen species (ROS) within levels compatible with signaling while ensuring robust and reliable energy supply.

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“…The net influx of adenine nucleotides in response to incubation with Ca2" occurred in the face of the greater concentrations of ATP and ADP than of PPi, and the reported low transport affinity for PP, compared with ATP in reconstituted vesicles (Kramer, 1985). However, since ATP, ADP and presumably PPi are translocated as the free anion (Duszynski & Wojtczak, 1975;Kramer, 1980), and a high proportion is complexed with Mg2+ in vivo, caution must be taken when extrapolating Km values based on total values to the situation in vivo. In addition, since the maximum translocation rate is high (Klingenberg, 1976;Stubbs et al, 1978;Stubbs, 1981), substitution of PPi for ATP in only a small fraction of the total exchange would result in a modest accumulation of adenine nucleotides in the matrix over a period of time.…”

Section: Role Of Ca2l and Pp1 In Mitochondrial Swellingmentioning

confidence: 99%

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

Davidson

Halestrap

1987

Biochemical Journal

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1. The matrix pyrophosphate (PPi) content of isolated energized rat liver mitochondria incubated in the presence of ATP, Mg2+, Pi and respiratory substrate was about 100 pmol/mg of protein. 2. After incubation with sub-micromolar [Ca2+], this was increased by as much as 300%. There was a correlation between the effects of Ca2+ on PPi and on the increase in matrix volume reported previously [Halestrap, Quinlan, Whipps & Armston (1986) Biochem. J. 236, 779-787]. Half-maximal effects were seen at 0.3 microM-Ca2+. 3. Coincident with these effects, the total adenine nucleotide content increased in a carboxyatractyloside-sensitive manner. 4. Incubation with 0.2-0.5 mM-butyrate induced similar but smaller effects on mitochondrial swelling and matrix PPi and total adenine nucleotide content. Addition of butyrate after Ca2+, or vice versa, caused Ca2+-induced mitochondrial swelling to stop or reverse, while matrix PPi increased 30-fold. 5. Addition of atractyloside or the omission of ATP from incubations greatly enhanced swelling induced by Ca2+ without increasing matrix PPi. 6. Swelling of mitochondria incubated under de-energized conditions in iso-osmotic KSCN was progressively enhanced by the addition of increasing concentrations of PPi (1-20 mM) or valinomycin. 7. In iso-osmotic potassium pyrophosphate swelling was slow initially, but accelerated with time. This acceleration was inhibited by ADP, whereas carboxyatractyloside induced rapid swelling. Swelling in other iso-osmotic PPi salts showed that the rate of entry decreased in the order NH4+ greater than K+ greater than Na+ greater than Li+, whereas choline, tetramethylammonium and Tris did not enter. It is suggested that the adenine nucleotide translocase transports small univalent cations when PPi is bound and that PPi can also be transported when the transporter is in the conformation induced by carboxyatractyloside. 8. It is concluded that Ca2+ and butyrate cause swelling of energized mitochondria through this effect of PPi on K+ permeability of the mitochondrial inner membrane. 9. Freeze-clamped livers from rats treated with glucagon or phenylephrine show 30-50% increases in tissue PPi. It is proposed that Ca2+-mediated increases in mitochondrial PPi are responsible for the increase in matrix volume and total adenine nucleotide content observed after hormone treatment.

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Effect of metal cations on the inhibition of adenine nucleotide translocation by acyl‐coa

Cited by 20 publications

References 12 publications

Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition

Increased Susceptibility of Striatal Mitochondria to Calcium-Induced Permeability Transition

Mitochondrial and cellular mechanisms for managing lipid excess

Liver mitochondrial pyrophosphate concentration is increased by Ca2+ and regulates the intramitochondrial volume and adenine nucleotide content

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