Thyroid hormone status and membrane n-3 fatty acid content influence mitochondrial proton leak.
Proton leak, as determined by the relationship between respiration rate and membrane potential, was lower in mitochondria from hypothyroid rats compared to euthyroid controls. Moreover, proton leak rates diminished even more when hypothyroid rats were fed a diet containing 5% of the lipid content as n-3 fatty acids. Similarly, proton leak was lower in euthyroid rats fed the 5% n-3 diet compared to one containing only 1% n-3 fatty acids. Lower proton leaks rates were associated with increased inner mitochondrial membrane levels of n-3 fatty acids and a decrease in the ratio of n-6/n-3 fatty acids. This trend was evident in the phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and cardiolipin phospholipid fractions. These results suggest that a significant portion of the effect of thyroid hormone status on proton leak is due to alterations in membrane fatty acid composition, primarily changes in n-3 content. Both the hypothyroid state and dietary effects appear to be mediated in part by inhibition of the Delta6- and Delta5-desaturase pathways.
Pehowich
D J
DJ
Department of Oral Health Sciences and Department of Medicine, Room 5145, Dent/Pharm Centre, University of Alberta, Edmonton, Alta. T6G 2N8, Canada. dpehowic@ualberta.ca
D000818:Animals; D004032:Diet; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors; D015525:Fatty Acids, Omega-3 / Q000032:analysis* / Q000494:pharmacology; D007037:Hypothyroidism / Q000378:metabolism*; D007425:Intracellular Membranes / Q000737:chemistry*; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry*; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010743:Phospholipids; D011522:Protons; D044943:Fatty Acid Desaturases