Decreased activity of the pyruvate translocator and changes in the lipid composition in heart mitochondria from hypothyroid rats.
A study of the transport of pyruvate in heart mitochondria from normal and hypothyroid rats has been carried out. Heart mitochondria from hypothyroid rats translocate pyruvate via the alpha-cyanocinnamate sensitive carrier much more slowly than do mitochondria from normal rats. Kinetic analysis of the pyruvate transport shows that the Vmax of this process is decreased while there is practically no change in the Km values. Neither a decrease in the transmembrane delta pH value nor a decrease in the total number of the pyruvate carrier molecules, titrated with labeled alpha-cyanocinnamate, account for the decreased rate of pyruvate transport. The lower activity of the pyruvate translocator in mitochondria from hypothyroid rats is associated with a parallel decrease of the rate of pyruvate supported oxygen uptake. There is, however, no difference in either the respiratory control ratios or in the ADP/O ratios between these two types of mitochondria. The heart mitochondrial lipid composition is significantly altered in hypothyroid rats. Cardiolipin, particularly, was found to decrease by around 36%. In addition the pattern of fatty acids was found to be altered in mitochondrial membranes from hypothyroid rats. It is suggested that the decreased activity of the pyruvate translocator in heart mitochondria from hypothyroid rats can be ascribed to changes in the lipid environment which surrounds the pyruvate carrier molecule in the mitochondrial membrane.
Paradies
G
G
Department of Biochemistry and Molecular Biology, Bari, Italy.
Ruggiero
F M
FM
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007037:Hypothyroidism / Q000378:metabolism*; D007425:Intracellular Membranes / Q000502:physiology; D007700:Kinetics; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008564:Membrane Potentials; D026901:Membrane Transport Proteins; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; D010101:Oxygen Consumption; D010743:Phospholipids / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D000070590:Solute Carrier Proteins
D002352:Carrier Proteins; D008563:Membrane Lipids; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; C000629174:Mpc1 protein, rat; D010743:Phospholipids; D011773:Pyruvates; D000070590:Solute Carrier Proteins