scholarly journals The mechanism of palmitoyl-CoA inhibition of Ca2+ uptake in liver and heart mitochondria

1981 ◽  
Vol 194 (1) ◽  
pp. 71-77 ◽  
Author(s):  
M C Beatrice ◽  
D R Pfeiffer
Keyword(s):  
Energy Source ◽  
Electron Transport ◽  
Membrane Permeability ◽  
Uptake Rate ◽  
Competitive Inhibitor ◽  
Heart Mitochondria ◽  
Ionophore A23187 ◽  
Inner Membrane

The mechanism by which palmitoyl-CoA inhibits Ca2+ uptake in liver and heart mitochondria was examined. At a given concentration of palmitoyl-CoA, the extent of inhibition is inversely related to the concentration of the respiratory substrate succinate. Palmitoyl-CoA inhibition of uncoupler-stimulated respiration and respiration stimulated by ionophore-A23187-induced Ca2+ cycling is also relieved by high succinate concentrations. These effects of palmitoyl-CoA and succinate concentration are distinct from the increase in inner-membrane permeability, which can be produced by palmitoyl-CoA and Ca2+ [Beatrice, Palmer & Pfeiffer (1980) J. Biol. Chem. 255, 8663-8671]. The apparent K0.5 of the mitochondrial Ca2+ pump is not altered by palmitoyl-CoA. No or negligible effects of palmitoyl-CoA on the Ca2+-uptake rate are observed when ascorbate replaces succinate as an energy source. These findings, together with the known activity of palmitoyl-CoA as a competitive inhibitor of the dicarboxylate carrier [Morel, Lauquin, Lunardi, Duszynski & Vignais (1974) FEBS Lett. 39, 133-138], indicate that palmitoyl-CoA inhibits energy-linked Ca2+ transport by limiting the rate of electron transport through limitation of succinate entry into the mitochondria rather than by directly inhibiting the Ca2+ carrier.

Involvement of SH-groups during interaction of diazoxide with the inner membrane of rat heart mitochondria

2007 ◽  
Vol 415 (1) ◽  
pp. 206-210 ◽  
Author(s):  
S. M. Korotkov ◽  
V. P. Nesterov ◽  
L. V. Emel’yanova ◽  
N. N. Ryabchikov
Keyword(s):  
Rat Heart ◽  
Heart Mitochondria ◽  
Inner Membrane ◽  
Sh Groups ◽  
Rat Heart Mitochondria

Dual Mutations Reveal Interactions Between Components of Oxidative Phosphorylation in Kluyveromyces lactis

Genetics ◽  
2001 ◽  
Vol 159 (3) ◽  
pp. 929-938
Author(s):  
G D Clark-Walker ◽  
X J Chen
Keyword(s):  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Kluyveromyces Lactis ◽  
Mitochondrial Protein ◽  
Proton Pumping ◽  
Nuclear Genes ◽  
Suppressor Activity ◽  
Inner Membrane ◽  
Atp Production

Abstract Loss of mtDNA or mitochondrial protein synthesis cannot be tolerated by wild-type Kluyveromyces lactis. The mitochondrial function responsible for ρ0-lethality has been identified by disruption of nuclear genes encoding electron transport and F0-ATP synthase components of oxidative phosphorylation. Sporulation of diploid strains heterozygous for disruptions in genes for the two components of oxidative phosphorylation results in the formation of nonviable spores inferred to contain both disruptions. Lethality of spores is thought to result from absence of a transmembrane potential, ΔΨ, across the mitochondrial inner membrane due to lack of proton pumping by the electron transport chain or reversal of F1F0-ATP synthase. Synergistic lethality, caused by disruption of nuclear genes, or ρ0-lethality can be suppressed by the atp2.1 mutation in the β-subunit of F1-ATPase. Suppression is viewed as occurring by an increased hydrolysis of ATP by mutant F1, allowing sufficient electrogenic exchange by the translocase of ADP in the matrix for ATP in the cytosol to maintain ΔΨ. In addition, lethality of haploid strains with a disruption of AAC encoding the ADP/ATP translocase can be suppressed by atp2.1. In this case suppression is considered to occur by mutant F1 acting in the forward direction to partially uncouple ATP production, thereby stimulating respiration and relieving detrimental hyperpolarization of the inner membrane. Participation of the ADP/ATP translocase in suppression of ρ0-lethality is supported by the observation that disruption of AAC abolishes suppressor activity of atp2.1.

scholarly journals A heart mitochondrial Ca2+-dependent pore of possible relevance to re-perfusion-induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states

1990 ◽  
Vol 266 (1) ◽  
pp. 33-39 ◽  
Author(s):  
M Crompton ◽  
A Costi
Keyword(s):  
Arsenazo Iii ◽  
Heart Mitochondria ◽  
Ionophore A23187 ◽  
Relative Permeabilities ◽  
Pulsed Flow ◽  
Pore Closure ◽  
Open States ◽  
Matrix Free ◽  
Pore Number

The permeability properties of a putative Ca2(+)-activated pore in heart mitochondria, of possible relevance to re-perfusion-induced injury, have been investigated by a pulsed-flow solute-entrapment technique. The relative permeabilities of [14C]mannitol, [14C]sucrose and arsenazo III are consistent with permeation via a pore of about 2.3 nm diameter. Ca2+ removal with EGTA induced pore closure, and the mitochondria became ‘resealed’. The permeability of the unresealed mitochondria during resealing was markedly stimulated by 200 microM-ADP, and the relative permeabilities to solutes of different size were stimulated equally, indicating an increase in open-pore number, rather than an increase in pore dimensions. This is paradoxical, since ADP also stimulated the rate of resealing. The rate of EGTA-induced resealing was also stimulated by the Ca2+ ionophore A23187, which indicates that the rate of removal of matrix free Ca2+ is limiting for pore closure. An explanation for the paradox is suggested in which ADP facilitates pore interconversion between the closed and open states in permeabilized mitochondria, and pore closure in Ca2(+)-free mitochondria occurs much faster than previously thought.

scholarly journals Blockade of Electron Transport at the Onset of Reperfusion Decreases Cardiac Injury in Aged Hearts by Protecting the Inner Mitochondrial Membrane

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Qun Chen ◽  
Thomas Ross ◽  
Ying Hu ◽  
Edward J. Lesnefsky
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Membrane Integrity ◽  
Reversible Inhibitor ◽  
Inner Mitochondrial Membrane ◽  
Inner Membrane ◽  
Fischer 344

Myocardial injury is increased in the aged heart following ischemia-reperfusion (ISC-REP) compared to adult hearts. Intervention at REP with ischemic postconditioning decreases injury in the adult heart by attenuating mitochondrial driven cell injury. Unfortunately, postconditioning is ineffective in aged hearts. Blockade of electron transport at the onset of REP with the reversible inhibitor amobarbital (AMO) decreases injury in adult hearts. We tested if AMO treatment at REP protects the aged heart via preservation of mitochondrial integrity. Buffer-perfused elderly Fischer 344 24 mo. rat hearts underwent 25 min global ISC and 30 min REP. AMO (2.5 mM) or vehicle was given for 3 min at the onset of REP. Subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria were isolated after REP. Oxidative phosphorylation (OXPHOS) and mitochondrial inner membrane potential were measured. AMO treatment at REP decreased cardiac injury. Compared to untreated ISC-REP, AMO improved inner membrane potential in SSM and IFM during REP, indicating preserved inner membrane integrity. Thus, direct pharmacologic modulation of electron transport at REP protects mitochondria and decreases cardiac injury in the aged heart, even when signaling-induced pathways of postconditioning that are upstream of mitochondria are ineffective.

scholarly journals Charge screening by cations affects the conformation of the mitochondrial inner membrane. A study of exogenous NAD(P)H oxidation in plant mitochondria

1981 ◽  
Vol 195 (3) ◽  
pp. 583-588 ◽  
Author(s):  
I M Møller ◽  
J M Palmer
Keyword(s):  
Electron Transport ◽  
Protein Complexes ◽  
Plant Mitochondria ◽  
Lateral Diffusion ◽  
Jerusalem Artichoke ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Cations caused a decrease in the apparent Km and an increase in the Vmax. for the oxidation of exogenous NADH by both Jerusalem-artichoke (Helianthus tuberosus) and Arum maculatum (cuckoo-pint) mitochondria prepared and suspended in a low-cation medium (approximately or equal to 1 mM-K+). In Arum mitochondria the addition of cations caused a much greater stimulation of the oxidation of NAD(P)H via the cytochrome oxidase pathway than via the alternative, antimycin-insensitive, pathway. This shows that cations affected a rate-limiting step in the electron-transport chain at or beyond ubiquinone, the branch-point of electron transport in plant mitochondria. The effects were only dependent on the valency of the cation (efficiency C3+ greater than C2+ greater than C+) and not on its chemical nature, which is consistent with the theory of the diffuse layer. The results are interpreted to show that the screening of fixed negative membrane changes on lipids and protein complexes causes a conformational change in the mitochondrial inner membrane, leading to a change in a rate-limiting step of NAD(P)H oxidation. More specifically, it is proposed that screening removes electrostatic restrictions on lateral diffusion and thus accelerates diffusion-limited steps in electron transport.

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