Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Biological Transport MeSH
- Guanosine Diphosphate pharmacology MeSH
- Adipose Tissue, Brown metabolism MeSH
- Ion Channels MeSH
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone pharmacology MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Cricetinae MeSH
- Mesocricetus MeSH
- Phenylpyruvic Acids pharmacology MeSH
- Carboxylic Acids metabolism MeSH
- Coumaric Acids pharmacology MeSH
- Lipid Bilayers MeSH
- Membrane Proteins metabolism MeSH
- Mitochondrial Proteins MeSH
- Mitochondria drug effects metabolism MeSH
- Monensin pharmacology MeSH
- Pyruvates metabolism MeSH
- Rotenone pharmacology MeSH
- Carrier Proteins metabolism MeSH
- Uncoupling Protein 1 MeSH
- Valinomycin pharmacology MeSH
- Mitochondrial Swelling drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Cricetinae MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-cyano-4-hydroxycinnamate MeSH Browser
- Guanosine Diphosphate MeSH
- Ion Channels MeSH
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone MeSH
- Phenylpyruvic Acids MeSH
- Carboxylic Acids MeSH
- Coumaric Acids MeSH
- Lipid Bilayers MeSH
- Membrane Proteins MeSH
- Mitochondrial Proteins MeSH
- Monensin MeSH
- phenylpyruvic acid MeSH Browser
- Pyruvates MeSH
- Rotenone MeSH
- Carrier Proteins MeSH
- Uncoupling Protein 1 MeSH
- Valinomycin MeSH
The physiological role of monocarboxylate transport in brown adipose tissue mitochondria has been reevaluated. We studied pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and phenylpyruvate uniport via the uncoupling protein (UCP1) as a GDP-sensitive swelling in K+ salts induced by valinomycin or by monensin and carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone in Na+ salts. We have demonstrated that this uniport is inhibited by fatty acids. GDP inhibition in K+ salts was not abolished by an uncoupler, indicating a negligible monocarboxylic acid penetration via the lipid bilayer. In contrast, the electroneutral pyruvate uptake (swelling in ammonium pyruvate or potassium pyruvate induced by change in pH) mediated by the pyruvate carrier was inhibited by its specific inhibitor alpha-cyano-4-hydroxycinnamate but not by fatty acids. Moreover, alpha-cyano-4-hydroxycinnamate enhanced the energization of brown adipose tissue mitochondria, which was monitored fluorometrically by 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide and safranin O. Consequently, we suggest that UCP1 might participate in futile cycling of unipolar ketocarboxylates under certain physiological conditions while expelling these anions from the matrix. The cycle is completed on their return via the pyruvate carrier in an H+ symport mode.
References provided by Crossref.org
Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling
Channel character of uncoupling protein-mediated transport