INITIATION OF MITOCHONDRIAL PROTEIN SYNTHESIS AT BIRTH † 1293

Abstract

We have observed that oxidative phosphorylation (OXPHOS) by isolated mitochondria (MITO) increases at birth in liver and kidney (Ped. Res. 37,214), but not heart (this meeting), and that newborn hypoxia prevents increased OXPHOS. To determine whether initiation of MITO biogenesis is also regulated by oxygen availability pre-term rabbit pups (30-31 days gestation, term=32 days) delivered by C-section were either sacrificed at birth (time zero) or maintained under normoxic (21% O2, NOX) or hypoxic(10% O2, HYPOX) conditions for 4 hours at 35° C. MITO were isolated and in-vitro protein synthesis (PS) determined by measuring 35S methionine incorporation. PS was greater in heart MITO from NOX vs HYPOX or time zero pups (113 ± 18 vs 55.2 ± 20 or 60.0 ± 13 CPM/ mg Prot / 30 min respectively, n=6, p < 0.05) while PS rate was similar for liver (48 ± 13 vs 47 ± 10 or 51.3 ± 11) and kidney (44.1± 15 vs 37.5 ± 20 or 39.5 ± 13) MITO. Nucleotide regulation of PS in NOX and HYPOX pups was also evaluated. PS was reduced by 40-50% (p < 0.05) when isolated MITO from heart, liver and kidney were incubated with 5 mM ATP + 1 mM GTP. Inhibition was similar in MITO from NOX and HYPOX pups. In summary, MITO biogenesis at birth is modulated by nucleotides in all organs and oxygen availability in heart, but not liver or kidney. Taken together these data demonstrate that metabolic adaptation at birth involve increased MITO OXPHOS or biogenesis, changes which are modulated by oxygenation in an organ specific manner.