Developmental Regulation of the α-Glycerophosphate Shuttle in Porcine Myocardium

Abstract

The α-glycerophosphate (α-GP) shuttle has been shown to play a role in reducing equivalent transfer in neonatal cardiac mitochondria. In adult heart mitochondria, α-GP shuttle activity is not detectable. The goals of the current study were to define the time course of the age-dependent decline in α-GP shuttle capacity and to identify the enzymatic step(s) of the α-GP shuttle which are regulated during development. Intact mitochondria were isolated from porcine hearts of various ages and assayed for α-GP shuttle capacity. By 5 weeks of age, α-GP shuttle capacity had decreased by nearly 39%. The cytosolic step of the shuttle, catalysed by cytosolic α-glycerophosphate dehydrogenase (cα-GPDH), demonstrated a significant increase between 0–2-day-old animals and adults. Partial cDNA clones of porcine cα-GPDH and mitochondrial α-glycerophosphate dehydrogenase (mα-GPDH) were prepared and used to quantitate expression of these genes. Using mRNA isolated from neonatal and adult porcine myocardium, expression of the cα-GPDH was unchanged, while expression of the mα-GPDH gene was present in neonatal but absent in adult myocardium. These results demonstrate a rapid postnatal decline in myocardial α-GP shuttle capacity which appears to be regulated by a decline in mα-GPDH gene expression.