Mitochondria Uncoupling by a Long Chain Fatty Acyl Analogue

Mitochondria uncoupling by fatty acids in vivo is still questionable, being confounded by their dual role as substrates for oxidation and as putative genuine uncouplers of oxidative phosphorylation. To dissociate between substrate and the uncoupling activity of fatty acids in oxidative phosphorylati...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 273; no. 7; pp. 3937 - 3942
Main Authors:	Hermesh, O, Kalderon, B, Bar-Tana, J
Format:	Journal Article
Language:	English
Published:	United States American Society for Biochemistry and Molecular Biology 13-02-1998
Subjects:	Animals Atractyloside - pharmacology Cell Respiration - drug effects Cells, Cultured Fatty Acids - pharmacology Flow Cytometry Hydrogen-Ion Concentration Membrane Potentials - drug effects Mitochondria, Heart - drug effects Mitochondria, Liver - drug effects Mitochondrial ADP, ATP Translocases - metabolism Oligomycins - pharmacology Oxidative Phosphorylation - drug effects Oxygen - metabolism Palmitic Acid - pharmacology Palmitic Acids - pharmacology Rats Uncoupling Agents - pharmacology
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Mitochondria uncoupling by fatty acids in vivo is still questionable, being confounded by their dual role as substrates for oxidation and as putative genuine uncouplers of oxidative phosphorylation. To dissociate between substrate and the uncoupling activity of fatty acids in oxidative phosphorylation, the uncoupling effect was studied here using a nonmetabolizable long chain fatty acyl analogue. Î²,Î²â²-Methyl-substituted hexadecane Î±,Ï-dioic acid (MEDICA 16) is reported here to induce in freshly isolated liver cells a saturable oligomycin-insensitive decrease in mitochondrial proton motive force with a concomitant increase in cellular respiration. Similarly, MEDICA 16 induced a saturable decrease in membrane potential, proton gradient, and proton motive force in isolated liver and heart mitochondria accompanied by an increase in mitochondrial respiration. Uncoupling by MEDICA 16 in isolated mitochondria was partially suppressed by added atractyloside. Hence, fatty acids may act as genuine uncouplers of cellular oxidative phosphorylation by interacting with specific mitochondrial proteins, including the adenine nucleotide translocase.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.273.7.3937