Abstract
This study investigated the developmental and nutritional programming of two important mitochondrial proteins, namely voltage-dependent anion channel (VDAC) and cytochrome c, in the sheep kidney, liver and lung. The effect of maternal nutrient restriction between early and mid-gestation (i.e. 28- to 80-day gestation, the period of maximal placental growth) on the abundance of these proteins was also examined in fetal and juvenile offspring. Fetuses were sampled at 80 and 140 days of gestation (term approximately 147 days), and postnatal animals at 1 and 30 days and 6 months of age. The abundance of VDAC peaked at 140 days of gestation in the lung, compared with 1 day after birth in the kidney and liver, whereas cytochrome c abundance was greatest at 140 days of gestation in the liver, 1 day after birth in the kidney and 6 months of age in lungs. This differential ontogeny in mitochondrial protein abundance between tissues was accompanied with very different tissue-specific responses to changes in maternal food intake. In the liver, maternal nutrient restriction only increased mitochondrial protein abundance at 80 days of gestation, compared with no effect in the kidney. In contrast, in the lung mitochondrial protein, abundance was raised near to term, whereas VDAC abundance was decreased by 6 months of age. These findings demonstrate the tissue-specific nature of mitochondrial protein development that reflects differences in functional adaptation after birth. The divergence in mitochondrial response between tissues to maternal nutrient restriction early in pregnancy further reflects these differential ontogenies.
Highlights
Mitochondria play a major role in regulating energy supply and related processes in most tissues
Maternal nutrient restriction had no effect on kidney weight or mitochondrial protein abundance at any sampling age, glucocorticoid receptor (GR) mRNA abundance was transiently raised in nutrient restricted (NR) fetuses at 140 days of gestation (Table 1)
Total weight was unaffected by maternal nutrition at all sampling ages, there was a reduction in total mitochondrial protein content at 80 days of gestation in the nutrient-restricted group that was accompanied by an up-regulation in the abundance of both voltagedependent anion channel (VDAC) and cytochrome c (Table 2)
Summary
Mitochondria play a major role in regulating energy supply and related processes in most tissues. This role is important at birth when the function of many fetal tissues has to adapt to the thermal, gaseous and metabolic challenges of the extrauterine environment (Gnanalingham et al 2005b, 2006). In precocious newborn, which have to establish metabolic and thermoregulatory independence at birth, uncoupling protein abundance in both adipose tissue and the lung peaks soon after parturition (Clarke et al 1997, Gnanalingham et al 2005c) and are critical in enabling the onset of nonshivering thermogenesis and lung maturation.
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