J. Biol. Chem., Vol. 265, Issue 22, 12910-12915, Aug, 1990

The mechanism of stimulation of respiration by fatty acids in isolated hepatocytes

CD Nobes, WW Hay Jr and MD Brand
Department of Biochemistry, University of Cambridge, United Kingdom.

Addition of fatty acids to isolated hepatocytes raised respiration rate by 92% and raised mitochondrial membrane potential (delta psi m) in situ from 155 to 162 mV suggesting that the increased fuel supply had a greater effect on respiration rate than any increases in processes that consumed mitochondrial protonmotive force (delta p). The relationship between delta psi m and respiration rate was changed by addition of fatty acids or lactate, showing that there was also stimulation of delta p-consuming reactions. In the presence of oligomycin the relationship between delta psi m and respiration rate was unaffected by substrate addition, showing that the kinetics of delta p consumption by the H+ leak across the mitochondrial inner membrane were unchanged. The stimulation of delta p consumers by fatty acids therefore must be in the pathways of ATP synthesis and turnover. Inhibition of several candidate ATP-consuming reactions had little effect on basal or fatty acid-stimulated respiration, and the nature of the ATP turnover reactions in hepatocytes remains speculative. We conclude that fatty acids (and other substrates) stimulate respiration in hepatocytes in two distinct ways. They provide substrate for the electron transport chain, raising delta p and increasing the non-ohmic proton leak across the mitochondrial inner membrane and the rate of oxygen consumption. They also directly stimulate an unidentified delta p-consuming reaction in the cytoplasm. They do not work by uncoupling or by stimulation of intramitochondrial ATP-turnover reactions.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Monemdjou, W. E. Hofmann, L. P. Kozak, and M.-E. Harper Increased mitochondrial proton leak in skeletal muscle mitochondria of UCP1-deficient mice Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E941 - E946. [Abstract] [Full Text] [PDF]

				D. G. Nicholls and S. L. Budd Mitochondria and Neuronal Survival Physiol Rev, January 1, 2000; 80(1): 315 - 360. [Abstract] [Full Text] [PDF]

				S. Monemdjou, L. P. Kozak, and M.-E. Harper Mitochondrial proton leak in brown adipose tissue mitochondria of Ucp1-deficient mice is GDP insensitive Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1073 - E1082. [Abstract] [Full Text] [PDF]

				M.-E. Harper, S. Monemdjou, J. J. Ramsey, and R. Weindruch Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E197 - E206. [Abstract] [Full Text] [PDF]

				O. Hermesh, B. Kalderon, and J. Bar-Tana Mitochondria Uncoupling by a Long Chain Fatty Acyl Analogue J. Biol. Chem., February 13, 1998; 273(7): 3937 - 3942. [Abstract] [Full Text] [PDF]