Expression of human cytochrome c, oxidase subunits during fetal development

Abstract

Expression of human cytochrome c oxidase (COX) subunits was examined at fetal (20-28 weeks) and adult state by Northern blot hybridization with mRNA from liver, heart, skeletal muscle, and intestine. The data were related to COX and citrate synthase activities and to immunodetected COX subunits (II/III, IV, VIIaH). In liver little changes of COX transcripts are observed from fetal to adult state. In contrast, in heart and skeletal muscle all transcripts of COX subunits increase between 2-20-fold, when related to the amount of 28s rRNA. In fetal heart and skeletal muscle the relative amounts of the liver-type transcripts of subunit VIa were 30% and 25% from total VIa transcripts (VIaL + VIaH), respectively, but decrease to only 2-5% at adult state. The liver-type transcripts of subunit VIIa occur to 50% in fetal heart and skeletal muscle, which remained unchanged in adult heart and decrease to 5 8 % in adult skeletal muscle. The results clearly indicate a switch of gene expression in heart and skeletal muscle during development, from the liver type to the headmuscle type of subunit VIa (and partly VIIa).Cytochrome c oxidase (COX) is the terminal enzyme complex of the respiratory chain, coupling the transfer of electrons from cytochrome c to molecular oxygen with the concomitant production of a proton electrochemical gradient across the inner mitochondrial membrane [l]. In mammals, the enzyme consists of 13 dissimilar polypeptides [ 2 ] . The three largest subunits (1-111) are encoded by the mitochondrial genome and constitute the catalytic core of the enzyme [3, 41. The ten smaller nuclear gene products [S] have been suggested to play a keyrole in the regulation of the enzyme [6, 71. Recently it was demonstrated [8, 91 that the activity and energy transduction of COX from heart and skeletal muscle is tissue-specific and regulated by nucleotides via interaction with subunit VIaH (heart/muscle type).The mammalian COX occurs in tissue-specific isoforms differing in the isotype of subunits VIa, VIIa and/or VIII (liver type or heart/muscle type). This has been demonstrated by immunological, electrophoretic and amino acid sequence differences between corresponding nuclear-coded subunits of COX from different mammalian tissues and species [2, 5, 101. These findings have been confirmed by cloning and sequencing of cDNAs coding for the different subunits of tissue-specific isoforms for subunit VIa of rat [ I l l , VIIa [lo,12, 161 and VIII [lo, 131 occur as liver (L) and heart (H) isoforms. In rat only the L form of subunit VIIa was found [17, 181, but both isoforms of subunits VIa [ l l ] and VIII [19]. In human, subunit VIII is present only in the L form [20, 211, whereas both isoforms occur for subunits VIa [22, Most of the other nuclearcoded subunits have been cloned and sequenced from rat, beef and human (for review see [28, 291).A co-ordinate expression of the mitochondrial-coded subunit 111 and the nuclear-coded subunit VIc has been demonstrated in rat tissues under steady-state conditions [30-321. Under non-s...

Influence of thyroid hormone on the tissue-specific expression of cytochrome c oxidase isoforms during cardiac development

“…We were able to confirm the tissue-specificity of the isoforms by performing Northern-blot analysis of various rat tissues. Similarly to previous findings in bovine [25,26,44], rat [22] and human [38], we found that the liver isoform of both subunits, VIII and VIa, was expressed at variable levels in liver, brain, lung, skeletal muscle, atria and ventricle tissues, whereas the heart isoform was expressed in the skeletal muscle, atria and ventricle tissues only (results not shown).…”

“…The heart isoforms of both VIa and VIII increase dramatically as development progresses from the fetal to the adult stage. Although the expression of the heart isoform has previously been shown to be highly up-regulated in bovine (VIa) and human (VIa and VIIa) hearts during development, the fetal hearts in these species already expressed the heart isoform in relatively large amounts [26,38], whereas our results in the rat demonstrated that the fetal heart expressed little (VIa) or no (VIII) heart isoform. The liver isoform was the predominant form of VIa and VIII in the fetal rat heart followed by a significant down-regulation as the rat approached adulthood.…”

“…The liver isoform was the predominant form of VIa and VIII in the fetal rat heart followed by a significant down-regulation as the rat approached adulthood. In contrast, in the bovine [26] and the human fetal heart [38], the VIa-liver isoform constituted only 25 and 30 % respectively, of the total amount of subunit VIa message. In summary, we determined quantitatively that there is an isoform transition in the rat heart during development, and the degree of this transition is much greater than that observed in other species.…”

“…Developmental regulation of COX subunit isoforms has been observed in human [38], bovine [26] and mouse [9] hearts. In the heart tissue, there is a switch in gene expression from the liver form to the heart form as the animal progresses from the fetal to the adult stage.…”

Mitonuclear coevolution as the genesis of speciation and the mitochondrial DNA barcode gap

“…2000) and at different developmental stages (Bonne et al. 1993). Isoforms enable control of ATP production and the membrane potential across variable conditions in different organs and tissues within an individual (Pierron et al.…”