Carnitine cycle in brown adipose tissue mitochondria as a tool for studying the regulatory role of fatty acids in the uncoupling protein function

• Published in: FEBS letters 1989-01, Vol.243 (1), p.37-40
• Main Authors: Ježek, Petr, Krasinskaya, Inna P., Smirnova, Ira, Drahota, Zdenék
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Adipose Tissue, Brown - metabolism; Animals; BAT, brown adipose tissue; Brown adipose tissue mitochondria; Carnitine - metabolism; Carrier Proteins; Cricetinae; DASMPI, 2-(p-dimethylaminostyryl)-1-methylpyridinium iodide; FA, fatty acid(s); Fatty acid uncoupling; Fatty Acids, Nonesterified - physiology; Guanosine Diphosphate - pharmacology; H + channel; Homeostasis; Ion Channels; Kinetics; Membrane Proteins - metabolism; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proteins; Oleic Acid; Oleic Acids - pharmacology; Oxygen Consumption - drug effects; PN, purine nucleotide; proteins; Uncoupling Agents - pharmacology; Uncoupling protein; Uncoupling Protein 1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(89)81213-X

A concerted function of purine nucleotide (PN) binding and fatty acid (FA) release from the uncoupling protein (UP) resulting in the maximum coupling (potential) of brown adipose tissue (BAT) mitochondria was demonstrated. The uncoupling effect of FA was studied (at 4 mM MgCl 2): 17 nmol oleate per mg protein caused a slight uncoupling with 8.9 mM ATP but with ATP below 3.6 mM almost total uncoupling was achieved. This shows that the PN-controlled gate can be stabilized in the closed conformation (with 8.9 mM ATP), also when FA is bound to UP. The sensitivity of the FA effect to ATP proves that oleate directly interacts with UP. The closed conformation of the H + channel of UP is then abolished by oleate when a lower free ATP concentration is maintained outside.