Deficiency of uncoupler-stimulated adenosine triphosphatase activity in tightly coupled hepatoma mitochondria

Proc Natl Acad Sci U S A. 1971 May;68(5):1079-82. doi: 10.1073/pnas.68.5.1079.

Abstract

Tightly coupled mitochondria from the well-differentiated hepatoma 7800 failed to exhibit a significant 2,4-dinitrophenol-activated ATPase activity at concentrations of uncoupler sufficient to completely inhibit oxidative phosphorylation. ATPase activity could not be maximally activated by uncoupling agents more potent than 2,4-dinitrophenol, such as carbonylcyanide p-trifluoromethoxyphenylhydrazone and 5-chloro, 3-tert-butyl, 2'-chloro, 4'-nitrosalicylanilide, nor by Mg(++) after the following treatments: sonication, freezing, detergent lysis, and digestion with trypsin. Gel electrophoresis patterns of the membrane proteins of the hepatome mitochondria revealed neither an absence of any one of the three different types of ATPase subunits characteristic of the homogeneous enzyme purified from normal liver mitochondria, nor a deficiency of the oligomeric molecule. Taken together, these data strongly suggest that the supramolecular structure of the membrane ATPase complex of mitochondria from hepatoma 7800 is altered in such a way that its capacity for ATP hydrolysis is severely diminished.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Animals
  • Carcinoma, Hepatocellular / enzymology*
  • Depression, Chemical
  • Dinitrophenols / pharmacology*
  • Electrophoresis
  • Liver Neoplasms
  • Male
  • Membranes / enzymology
  • Mitochondria, Liver / enzymology*
  • Neoplasms, Experimental
  • Oxidative Phosphorylation / drug effects
  • Oxidoreductases / antagonists & inhibitors
  • Rats
  • Stimulation, Chemical
  • Uncoupling Agents / pharmacology

Substances

  • Dinitrophenols
  • Uncoupling Agents
  • Oxidoreductases
  • Adenosine Triphosphatases