Postnatal expression and activity of the mitochondrial 2-oxoglutarate-malate carrier in intact hearts.
This study examines the functional implications of postnatal changes in the expression of the mitochondrial transporter protein, 2-oxoglutarate-malate carrier (OMC). Online (13)C nuclear magnetic resonance ((13)C NMR) measurements of isotope kinetics in hearts from neonate (3-4 days) and adult rabbits provided tricarboxylic acid cycle flux rates and flux rates through OMC. Neonate and adult hearts oxidizing 2.5 mM [2,4-(13)C(2)]butyrate were subjected to either normal or high cytosolic redox state (2.5 mM lactate) conditions to evaluate the recruitment of malate-aspartate activity and the resulting OMC flux. During development from neonate (3-4 days) to adult, mitochondrial protein density in the heart increased from 19 +/- 3% to 31 +/- 2%, whereas OMC expression decreased by 65% per mitochondrial protein content (P < 0.05). Correspondingly, OMC flux was lower in adults hearts than in neonates by 73% (neonate = 7. 4 +/- 0.4, adult = 2.0 +/- 0.1 micromol/min per 100 mg mitochondrial protein; P < 0.05). Despite clear changes in OMC content and flux, the responsiveness of the malate-aspartate shuttle to increased cytosolic NADH was similar in both adults and neonates with an approximate threefold increase in OMC flux (in densitometric units/100 mg mitochondrial protein: neonate = 25.8 +/- 2.5, adult = 6.0 +/- 0.2; P < 0.05). The (13)C NMR data demonstrate that OMC activity is a principal component of the rate of labeling of glutamate.
Griffin
J L
JL
Departments of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
O'Donnell
J M
JM
White
L T
LT
Hajjar
R J
RJ
Lewandowski
E D
ED
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006321:Heart / Q000254:growth & development; D066298:In Vitro Techniques; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D011817:Rabbits
D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C066909:2-oxoglutarate-malate carrier protein; D019344:Lactic Acid; D018698:Glutamic Acid