Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system?
One of the many functions of liver peroxisomes is the beta-oxidation of long-chain fatty acids. It is essential for the continuation of peroxisomal beta-oxidation that a redox shuttle system exist across the peroxisomal membrane to reoxidize NADH. We propose that this redox shuttle system consists of a substrate cycle between lactate and pyruvate. Here we present evidence that purified peroxisomal membranes contain both monocarboxylate transporter 1 (MCT 1) and MCT 2 and that along with peroxisomal lactate dehydrogenase (pLDH) form a Peroxisomal Lactate Shuttle. Peroxisomal beta-oxidation was greatly stimulated by the addition of pyruvate and this increase was partially inhibited by the addition of the MCT blocker alpha-cyano-4-hydroxycinnamate (CINN). We also found that peroxisomes generated lactate in the presence of pyruvate. Together these data provide compelling that the Peroxisome Lactate Shuttle helps maintain organelle redox and the proper functioning of peroxisomal beta-oxidation.
McClelland
Grant B
GB
Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, CA 94720-3140, USA.
Khanna
Savita
S
González
Gilda F
GF
Butz
C Eric
CE
Brooks
George A
GA
D000818:Animals; D001692:Biological Transport; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
D005227:Fatty Acids; D007770:L-Lactate Dehydrogenase; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D019289:Pyruvic Acid; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C091633:Slc16a7 protein, rat