Abstract
Reduced glutathione, in concentrations approximating those occurring in intact rat liver, causes swelling of rat liver mitochondria in vitro which is different in kinetics and extent from that yielded by L-thyroxine. The effect is also given by cysteine, which is more active, and reduced coenzyme A, but not by L-ascorbate, cystine, or oxidized glutathione. The optimum pH is 6.5, whereas thyroxine-induced swelling is optimal at pH 7.5. The GSH-induced swelling is not inhibited by DNP or dicumarol, nor by high concentrations of sucrose, serum albumin, or polyvinylpyrrolidone, in contrast to thyroxine-induced swelling. ATP inhibits the GSH swelling, but ADP and AMP are ineffective. Mn-+ is a very potent inhibitor, but Mg++ is ineffective. Ethylenediaminetetraacetate is also an effective inhibitor of GSH-induced swelling. The respiratory inhibitors amytal and antimycin A do not inhibit the swelling action of GSH, but cyanide does; these findings are consistent with the view that the oxidation-reduction state of the respiratory chain between cytochrome c and oxygen is a determinant of GSH-induced swelling. Reversal of GSH-induced swelling by osmotic means or by ATP in KCl media could not be observed. Large losses of nucleotides and protein occur during the swelling by GSH, suggesting that the action is irreversible. The characteristically drastic swelling action of GSH could be prevented if L-thyroxine was also present in the medium.
Full Text
The Full Text of this article is available as a PDF (657.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BARTLEY W., AMOORE J. E. The effects of manganese on the solute content of rat-liver mitochondria. Biochem J. 1958 Jul;69(3):348–360. doi: 10.1042/bj0690348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHAPPELL J. B., GREVILLE G. D. Dependence of mitochondrial swelling on oxidizable substrates. Nature. 1958 Sep 20;182(4638):813–814. doi: 10.1038/182813a0. [DOI] [PubMed] [Google Scholar]
- COTTONE M. A., WITTER R. F. The effect of lysolecithin and related compounds on the swelling of isolated mitochondria. Biochim Biophys Acta. 1956 Nov;22(2):372–377. doi: 10.1016/0006-3002(56)90165-2. [DOI] [PubMed] [Google Scholar]
- DAVIES R. E., FONNESU A., PRICE C. A. Movements of water and ions in mitochondria. Biochem J. 1956 Dec;64(4):754–768. doi: 10.1042/bj0640754. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIES R. E., FONNESU A. The prevention of swelling of liver mitochondria in vitro. Biochem J. 1956 Dec;64(4):769–777. doi: 10.1042/bj0640769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DICKENS F., SALMONY D. Effects of thyroid hormones in vitro on tissue respiration, oxidative phosphorylation and the swelling of mitochondria. Biochem J. 1956 Dec;64(4):645–651. doi: 10.1042/bj0640645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EMMELOT P., BOS C. J. Thyroxine-mediated release of diphosphopyridine nucleotide from mitochondrial dehydrogenases. Exp Cell Res. 1958 Feb;14(1):132–141. doi: 10.1016/0014-4827(58)90219-2. [DOI] [PubMed] [Google Scholar]
- FRIEDKIN M., LEHNINGER A. L. Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen. J Biol Chem. 1949 Apr;178(2):611–644. [PubMed] [Google Scholar]
- HUNTER F. E., Jr, FORD L. Inactivation of oxidative and phosphorylative systems in mitochondria by preincubation with phosphate and other ions. J Biol Chem. 1955 Sep;216(1):357–369. [PubMed] [Google Scholar]
- LEHNINGER A. L., RAY B. L. Oxidation-reduction state of rat liver mitochondria and the action of thyroxine. Biochim Biophys Acta. 1957 Dec;26(3):643–644. doi: 10.1016/0006-3002(57)90115-4. [DOI] [PubMed] [Google Scholar]
- LEHNINGER A. L., RAY B. L., SCHNEIDER M. The swelling of rat liver mitochondria by thyroxine and its reversal. J Biophys Biochem Cytol. 1959 Jan 25;5(1):97–108. doi: 10.1083/jcb.5.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEHNINGER A. L., UL HASSAN M., SUDDUTH H. C. Phosphorylation coupled to the oxidation of ascorbic acid by isolated mitochondria. J Biol Chem. 1954 Oct;210(2):911–922. [PubMed] [Google Scholar]
- LINDBERG O., ERNSTER L. Manganese, a co-factor of oxidative phosphorylation. Nature. 1954 May 29;173(4413):1038–1039. doi: 10.1038/1731038a0. [DOI] [PubMed] [Google Scholar]
- LIPMANN F., MERIWETHER B. P., MUDD S. H., PARK C. R., PARK J. H. Glutathione and ethylenediaminetetraacetate antagonism of uncoupling of oxidative phosphorylation. Biochim Biophys Acta. 1956 Nov;22(2):403–404. doi: 10.1016/0006-3002(56)90174-3. [DOI] [PubMed] [Google Scholar]
- MALEY G. F., LARDY H. A. Phosphorylation coupled with the oxidation of reduced cytochrome c. J Biol Chem. 1954 Oct;210(2):903–909. [PubMed] [Google Scholar]
- RAAFLAUB J. Die Schwellung isolierter Leberzellmitochondrien und ihre physikalisch-chemische Beeinflussbarkeit. Helv Physiol Pharmacol Acta. 1953;11(2):142–156. [PubMed] [Google Scholar]
- SLATER E. C., CLELAND K. W. The effect of calcium on the respiratory and phosphorylative activities of heart-muscle sarcosomes. Biochem J. 1953 Nov;55(4):566–590. doi: 10.1042/bj0550566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TAPLEY D. F. The effect of thyroxine and other substances on the swelling of isolated rat liver mitochondria. J Biol Chem. 1956 Sep;222(1):325–339. [PubMed] [Google Scholar]