Long-chain fatty acids act as protonophoric uncouplers of oxidative phosphorylation in rat liver mitochondria.
The effect of long-chain fatty acids (LCFA) on respiration and transmembrane potential (delta psi) in the resting state, and the rate of delta psi dissipation [d delta psi/dt)i) was investigated with oligomycin-inhibited rat liver mitochondria using succinate (plus rotenone) as substrate. The results obtained were compared with those of classical protonophores such as 2,4-dinitrophenol (DNP) and 4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazole (TTFB). The effects of oleate or palmitate and that of DNP or TTFB on respiration and delta psi can be described by a common force-flow relationship. These facts all in all are not compatible with a decoupler-type uncoupling mechanism of LCFA; still, they indicate that the latter are protonophores. Moreover, the oleate-induced increase in the rate of delta psi dissipation closely correlates with that in respiration, suggesting that the uncoupling activity and the protonophoric activity of LCFA are interrelated. Carboxyatractyloside (CAT) exerted only a small inhibitory effect on oleate-induced respiration and delta psi dissipation, indicating that the adenine nucleotide translocase contributes to the uncoupling effect of LCFA to a minor extent only. Proton transport through the lipid region of the membrane as mediated by permeation of the protonated and deprotonated forms of LCFA is interpreted as the main process of the uncoupling of LCFA.
Schönfeld
P
P
Institut für Biochemie der Medizinischen Akademie Magdeburg, G.D.R.
Schild
L
L
Kunz
W
W
D019297:2,4-Dinitrophenol; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001692:Biological Transport; D004140:Dinitrophenols / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D011522:Protons; D051381:Rats; D014475:Uncoupling Agents / Q000494:pharmacology*
D001562:Benzimidazoles; D004140:Dinitrophenols; D005227:Fatty Acids; D009829:Oleic Acids; D009840:Oligomycins; D010169:Palmitic Acids; D011522:Protons; D014475:Uncoupling Agents; D001278:Atractyloside; C005817:4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazole; D019301:Oleic Acid; D019308:Palmitic Acid; D000226:Mitochondrial ADP, ATP Translocases; D019297:2,4-Dinitrophenol; C003853:carboxyatractyloside