Mechanisms for the transport of alpha,omega-dicarboxylates through the mitochondrial inner membrane.
alpha,omega-Dicarboxylates have antibacterial properties, have been used in the treatment of hyperpigmentary disorders, are active against various melanoma cell lines, and can also undergo beta-oxidation. Little, however, is known about their transport. In this paper, we examine the mitochondrial transport of alpha, omega-dicarboxylates ranging from oxalate (DC2) to sebacate (DC10). DC2-DC10 are transported by the inner membrane anion channel (IMAC). DC6-DC10 are also transported by an electroneutral mechanism that appears to reflect transport of the acid through the lipid bilayer. At 37 degrees C and pH 7.0, DC10 is transported very rapidly at 3 micromol/min.mg, and respiring mitochondria swell in the K+ salts of these acids. This transport mechanism is probably the major pathway by which the longer dicarboxylates enter cells, bacteria, and mitochondria. We also demonstrate that DC5-DC10 can also be transported by an electroneutral mechanism mediated by tributyltin, a potent inhibitor of IMAC. The mechanism appears to involve electroneutral exchange of a TBT-dicarboxylate-H complex for TBT-OH. Finally, we present evidence that of all the dicarboxylates tested only DC2-DC4 can be transported by the classical dicarboxylate carrier.
Liu
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G
Department of Pharmacology, Medical College of Ohio, Toledo, Ohio 43699-0008, USA.
Hinch
B
B
Beavis
A D
AD
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D003652:Decanoic Acids / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010070:Oxalates / Q000378:metabolism; D018272:Porins; D013329:Structure-Activity Relationship; D050994:Voltage-Dependent Anion Channels
D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D007473:Ion Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010070:Oxalates; D018272:Porins; D050994:Voltage-Dependent Anion Channels; C011107:sebacic acid