Postnatal mitochondrial differentiation in rat liver. Regulation by thyroid hormones of the beta-subunit of the mitochondrial F1-ATPase complex.
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., Satrústegui, 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.
Izquierdo
J M
JM
Departamento de Biología Molecular, Universidad Autónoma de Madrid, Spain.
Luis
A M
AM
Cuezva
J M
JM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007037:Hypothyroidism / Q000139:chemically induced / Q000201:enzymology; D007163:Immunosorbent Techniques; D008099:Liver / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D008431:Maternal-Fetal Exchange; D008713:Methimazole; D008930:Mitochondria, Liver / Q000502:physiology*; D008970:Molecular Weight; D011247:Pregnancy; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis; D006180:Proton-Translocating ATPases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D011498:Protein Precursors; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D008713:Methimazole; D006180:Proton-Translocating ATPases; D013974:Thyroxine