Heart mitochondrial DNA and enzyme changes during early human development

Previous studies in our laboratory demonstrated significant changes in bovi ne heart mitochondrial bioenergetics during fetal growth and development. T o further understand mitochondrial biogenesis in early human development, t he activity and subunit content levels of specific mitochondrial enzymes in fetal and neonatal heart were determined. Comparing early gestation (EG, 4 5-65 day) later gestation (LG, 85-110 day) and neonate (birth-1 month), spe cific activity of citrate synthase (CS), a Krebs cycle enzyme showed a 2 fo ld increase from EG to LG and a 2 fold increase from LG to neonate. Specifi c activities of complex IV and complex V increased similarly 1.8-2 fold fro m EG to LG. However during the later fetal period from LG to neonate, compl ex IV activity increased only 1.3 fold and complex V showed no significant increase. Peptide content of COX-II subunit increased 2 fold from EG to LG and by 3.5 fold from LG to neonate. Levels of COX-IV and ATP synthase alpha subunits were undetectable in EG hearts, clearly detectable in LG heart an d 3 fold increased from LG to neonate. Unexpectedly, mitochondrial transcri ption factor A (mt-TFA) levels were not significantly different during thes e developmental stages. Mitochondrial DNA (mtDNA) levels increased 1.8 fold from EG to LG, and 3.8 fold increase from EG to neonate and correlated wit h CS activity levels. In conclusion, these data indicate coordinated regula tion of some nuclear-encoded (COX-IV and CS activity) and mitochondrial com ponents (COX-II and mtDNA), and strongly suggest that mitochondrial content increases particularly during the early fetal cardiac development and reve al a distinct pattern of regulation for mt-TFA.