Postnatal expression and activity of the mitochondrial 2-oxoglutarate-malate carrier in intact hearts

Am J Physiol Cell Physiol. 2000 Dec;279(6):C1704-9. doi: 10.1152/ajpcell.2000.279.6.C1704.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Citric Acid Cycle / physiology
  • Glutamic Acid / metabolism
  • Heart / growth & development
  • In Vitro Techniques
  • Kinetics
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy
  • Mitochondria / metabolism*
  • Mitochondrial Proteins
  • Myocardium / metabolism*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Rabbits

Substances

  • Carrier Proteins
  • Mitochondrial Proteins
  • 2-oxoglutarate-malate carrier protein
  • Lactic Acid
  • Glutamic Acid