Ontogeny of malate-aspartate shuttle capacity and gene expression in cardiac mitochondria.
Developmental downregulation of the malate-aspartate shuttle has been observed in cardiac mitochondria. The goals of this study were to determine the time course of the postnatal decline and to identify potential regulatory sites by measuring steady-state myocardial mRNA and protein levels of the mitochondrial proteins involved in the shuttle. By use of isolated porcine cardiac mitochondria incubated with saturating concentrations of the cytosolic components of the malate-aspartate shuttle, shuttle capacity was found to decline by approximately 50% during the first 5 wk of life (from 921 +/- 48 to 531 +/- 53 nmol.min-1.mg protein-1). Mitochondrial aspartate aminotransferase mRNA levels were greater in adult than in newborn myocardium. mRNA levels of mitochondrial malate dehydrogenase in adult cardiac tissue were 224% of levels in newborn tissue, whereas protein levels were 54% greater in adult myocardium. Aspartate/glutamate carrier protein levels were also greater in adult than in newborn tissue. mRNA and protein levels of the oxoglutarate/malate carrier were increased in newborn myocardium. It was concluded that 1) myocardial malate-aspartate shuttle capacity declines rapidly after birth, 2) divergence of mitochondrial malate dehydrogenase mRNA and protein levels during development suggests posttranscriptional regulation of this protein, and 3) the developmental decline in malate-aspartate shuttle capacity is regulated by decreased oxoglutarate/malate carrier gene expression.
Scholz
T D
TD
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Koppenhafer
S L
SL
tenEyck
C J
CJ
Schutte
B C
BC
D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D008291:Malate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008293:Malates / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D018076:DNA, Complementary; D008293:Malates; D012333:RNA, Messenger; D009243:NAD; D001224:Aspartic Acid; C030298:malic acid; D008291:Malate Dehydrogenase; D001219:Aspartate Aminotransferases