Increase in mitochondrial content of long-chain acyl-CoA in brown adipose tissue during cold-acclimation.
The mitochondrial content of long-chain acyl-CoA esters in the brown adipose tissue of guinea pigs increased 3.5-fold from a level of 92 +/- 17 pmol per mg protein (+/- S.E.; n = 7) in the control animals adapted at 22 degrees C to a new steady-state level of 328 +/- 20 pmol per mg protein (+/- S.E.; n = 46) after 10 days of cold-acclimation (5 degrees C). These low values of long-chain acyl-CoA species and the slow adaptive response for their increase do not support the proposal (Cannon, B., Sindin, U. and Romert, L. (1977) FEBS Lett. 4, 43-46) that the fatty acid CoA-esters have a physiological function in the regulation of the H+ (or OH-) permeability of the mitochondrial inner membrane. Experimental evidence is presented supporting the proposal that the long-chain acyl-CoA species are largely confined to the cytosolic side of the inner membrane. The activity of the adenine nucleotide translocase, as estimated at 25 degrees C in the reverse direction, was found to increase 5-fold upon depletion of the mitochondria of fatty acids (free and esterified) by preincubation with bovine serum albumin. The presence of potent inhibitors, i.e., long-chain acyl-CoA species, of adenine nucleotide translocation in brown adipose tissue of thermogenically active animals further supports the conclusion that ATP hydrolyzing mechanisms contribute insignificantly to long-term thermogenesis. The low values of long-chain acyl-CoA hydrolase (EC 3.1.2.1) activity, as measured in intact mitochondria and on a mitochondrial matrix fraction (i.e., 1.6 nmol X min-1 per mg protein), do not support the proposal that the hydrolase activity plays a significant role in the loose-coupling of brown adipose tissue mitochondria, either by a futile cycle mechanism or promoted by free fatty acid-induced uncoupling.
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000648:ultrastructure*; D000818:Animals; D002451:Cell Compartmentation; D003080:Cold Temperature; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D013053:Spectrophotometry
D000214:Acyl Coenzyme A; C017585:oleoyl-coenzyme A; D006160:Guanosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D010170:Palmitoyl-CoA Hydrolase