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J. Biol. Chem., Vol. 265, Issue 16, 9090-9097, Jun, 1990
JM Izquierdo, AM Luis and JM Cuezva
Postnatal development of rat liver mitochondrial functions, i.e.
differentiation of pre-existing mitochondria, is a key regulatory process
that is accomplished during the first postnatal hour (Valcarce, C.,
Navarrete, R. M., Encabo, P., Loeches, E., Satrustegui, J., and Cuezva, J.
M. (1988) J. Biol. Chem. 263, 7767-7775). The general mechanism that
appears to control this process is the rapid (2-fold) increase in inner
mitochondrial membrane proteins, as a result of a rapid increase in the
rates of protein synthesis for mitochondrial proteins. Fetal hypothyroidism
induced by administration of methimazole to pregnant rats resulted in half
the ATPase activity and amount of beta-F1-ATPase protein in liver
homogenates compared with normal fetuses. Furthermore, hypothyroid neonates
showed no postnatal increase in the amount of mitochondrial beta subunit of
the F1-ATPase complex. Administration of thyroid hormones to hypothyroid
neonates at birth promoted a 2-fold increase in liver ATPase activity and
in the amount of beta-F1-ATPase protein both in liver homogenates and in
isolated mitochondria. The rapid increase in beta-F1-ATPase protein
observed in thyroid hormone-treated hypothyroid neonates was paralleled by
a 2-fold increase in the relative rates of beta-F1-ATPase synthesis and by
a 2- fold increase in the relative amount of hepatic beta-F1-ATPase mRNA.
The results show that the basal expression of the beta-F1-ATPase gene is
regulated by thyroid hormones at either a transcriptional and/or
post-transcriptional level. Thus, these results show the requirement of
thyroid hormones for proliferation and differentiation of mitochondria in
the fetal and neonatal liver, respectively. On the other hand, the fact
that liver mRNA level of beta-F1-ATPase protein does not change between 0
and 1 postnatal h in the normal neonatal liver indicates that postnatal
mitochondrial differentiation is regulated at a translational level.
Postnatal mitochondrial differentiation in rat liver. Regulation by thyroid hormones of the beta-subunit of the mitochondrial F1-ATPase complex
Departamento de Biologia Molecular, Universidad Autonoma de Madrid, Spain.
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