1. In rat liver mitochondria in state 1 or 4 there is a permeability barrier against cystamine, probably in the inner membrane. 2. The permeability barrier was broken (a) when oxidative phosphorylation was uncoupled, (b) when the respiratory chain was inhibited or in anaerobiosis, or (c) when phosphate was added in the absence of exogenous substrate. Under these conditions increased amounts of [(35)S]cystamine residues were bound to matrix proteins. 3. It appears that the permeability barrier against cystamine in mitochondria reflects a ;high-energy state'. A gradual increase in the permeability for cystamine strikingly coincided with the loss of respiratory control induced by increasing concentrations of different uncoupling agents. 4. Cystamine caused uncoupling of oxidative phosphorylation in state 2 or 5, but not in state 1, 3 or 4. The uncoupling effect of cystamine was dependent on the phosphorylation potential. ATP counteracted, whereas ADP potentiated, the uncoupling by cystamine. 5. The variable penetration of cystamine appears to depend on its positive charge, since a dication derivative, NNN'N'-tetramethylcystamine, has a similar pattern of penetration, whereas an uncharged derivative, NN'-diacetylcystamine, penetrates rapidly into mitochondria irrespective of their metabolic state. 6. It is suggested that a charge barrier is present in or across the inner mitochondrial membrane in ;high-energy states'.

Journal Article↗

PubMed1968

The mechanism of disulphide reduction by mitochondria.

1. Cystamine was reduced to the corresponding thiol by rat liver mitochondria, even in the presence of rotenone or antimycin A. 2. The reduction of disulphides was stimulated by the accumulation of NADH or by the addition of NADH to osmotically ;shocked' mitochondria. 3. Energy made available by oxidative phosphorylation was not essential for the reduction of disulphides. 4. Cystamine was not reduced during the oxidation of NADH by ultrasonically treated particles, which had lost their capacity for oxidation of alpha-oxo acids. 5. In intact mitochondria, arsenite and other inhibitors of vicinal dithiols caused a decrease in the capacity for reduction of disulphides concomitantly with an inhibition of the oxidation of alpha-oxo acids. 6. Isolated lipoamide dehydrogenase reduced cystamine at the expense of NADH, provided that lipoic acid was also present. 7. It is concluded that in mitochondria the reduction of cystamine and related disulphides is probably brought about by interaction with reduced lipoic acid, generated by the alpha-oxo acid dehydrogenase complexes during the oxidation of alpha-oxo acids or by reaction of lipoamide dehydrogenase with NADH.

Animals↗

PubMed1966

Effects of cystamine and cysteamine on the adenosine-triphosphatase activity and oxidative phosphorylation of rat-liver mitochondria.

1. Cystamine (2,2'-diaminodiethyl disulphide) caused an unmasking of mitochondrial adenosine triphosphatase and a leakage of Mg(2+) from the mitochondria, and decreased the stimulation of adenosine triphosphatase by 2,4-dinitrophenol. When Mg(2+) was added, cystamine potentiated the activation of adenosine triphosphatase by 2,4-dinitrophenol. 2. Cystamine was without effect on the adenosine triphosphatase of disrupted mitochondria. 3. Cystamine was moderately potent as an uncoupling agent and as an inhibitor of the [(32)P]P(i)-ATP exchange reaction. 4. Cysteamine (2-aminoethanethiol) was without the above effects, when special precautions were taken to counteract its autoxidation. 5. The effects of cystamine should probably be ascribed to its disulphide group, since the diamine cadaverine protected slightly against the loss of Mg(2+) and the decrease of 2,4-dinitrophenol-stimulated adenosine-triphosphatase activity caused by aging of the mitochondria. It is suggested that cystamine acts by a breakdown of mitochondrial permeability barriers.

Adenosine Triphosphatases↗

PubMed1966

Effects of cystamine and cysteamine on the peroxidation of lipids and the release of proteins from mitochondria.

1. Cystamine slightly stimulated the peroxidation of lipids in mitochondria. Maximal effects were obtained at low concentrations (0.5mm). 2. Cysteamine, when allowed to autoxidize, had much stronger effects than cystamine. 3. Cysteamine and GSH did not induce peroxidation when their autoxidation was counteracted. 4. When kept reduced, cysteamine prevented the ascorbate-induced peroxidation of lipids. GSH was less efficient. 5. Cystamine as well as cysteamine prevented the loss of proteins from mitochondria induced by ascorbate, whereas cadaverine, GSSG and GSH were inefficient.

Animals↗

PubMed1966

Bacteria in Whipple's disease. Isolation of a Haemophilus strain from the jejunal propria.

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Adrenal Glands↗