Abstract
Mitochondrial Creatine Kinase (MtCK) is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine, and exists in mammals as two isoenzymes encoded by separate genes. In rats and humans, sarcomere-specific MtCK (sMtCK) is expressed only in skeletal and heart muscle, and has 87% nucleotide identity across the 1257 bp coding region. The ubiquitous isoenzyme of MtCK (uMtCK) is expressed in many tissues with highest levels in brain, gut, and kidney, and has 92% nucleotide identity between the 1254 bp coding regions of rat and human. Both genes are highly regulated developmentally in a tissue-specific manner. There is virtually no expression of sMtCK mRNA prior to birth. Unlike cytosolic muscle CK (MCK) and brain CK (BCK), there is no developmental isoenzyme switch between the MtCKs. Cell culture models representing the tissue-specific expression of either sMtCK or uMtCK are available, but there are no adequate developmental models to examine their regulation. Several animal models are available to examine the coordinate regulation of the CK gene family and include 1) Cardiac Stress by coarctation (sMtCK, BCK, and MCK), 2) Uterus and placenta during pregnancy (uMtCK and BCK), and 3) Diabetes and mitochondrial myopathy (sMtCK, BCK, and MCK). We report the details of these findings, and discuss the coordinate regulation of the genes necessary for high-energy transduction.
Similar content being viewed by others
References
Tzagoloff A, Meyers AM: Genetics of mitochondrial biogenesis. Annu Rev Biochem 55:249–285, 1968
Haas RC, Korenfeld C, Zhang Z, Perryman B, Roman D, Strauss AW: Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase. J Biol Chem 264:2890–2897, 1989
Haas RC, Strauss AW: Separate nuclear genes encode sarcomerespecific and ubiquitous human mitochondrial creatine kinase isoenzymes. J Biol Chem 265:6921–6927, 1990
Payne RM, Haas RC, Strauss AW: Structural characterization and tissue-specific expression of the mRNAs encoding isoenzymes from two rat mitochondrial creatine kinase genes. Biochim Biophys Acta 1089:352–361, 1991
Trask RV, Billadello JJ: Tissue-specific distribution and developmental regulation of M and B creatine kinase mRNAs. Biochim Biophys Acta 1049:182–188, 1990
Maciejewski-Lenoir D, Jirikowski GF, Sanna PP, Bloom FE: Reduction of exogenous vasopressin RNA poly(A) tail length increases its effectiveness in transiently correcting diabetes insipidus in the Brattleboro rat. Proc Natl Acad Sci USA 90:1435–1439, 1993
Smith AF: Separation of tissue and serum creatine kinase isoenzymes on polyacrylamide gel slabs. Clin Chem Acta 39:351, 1972
Hall N, DeLuca M: Developmental changes in creatine phosphokinase isoenzymes in neonatal mouse hearts. Biochem Biophys Res Commun 66:988–994, 1975
Payne RM, Friedman DL, Grant JW, Perryman MB, Strauss AW: Creatine kinase isoenzymes are highly regulated during pregnancy in rat uterus and placenta. Amer J Physiol 265 (Endocrinol Metab 28):E624-E635, 1993
Norwood WI, Ingwall JS, Norwood CR, Fossel ET: Developmental changes of creatine kinase metabolism in rat brain. Am J Physiol 244:C205-C210, 1983
Hoerter JA, Kuznetsov A, Ventura-Clapier R: Functional development of the creatine kinase system in perinatal rabbit heart. Circ Res 69:665–676, 1991
Lunardi J, Hurko O, Engel WK, Attardi G: The multiple ADP/ATP translocase genes are differentially expressed during human muscle development. J Biol Chem 267:15267–15270, 1992
Kuznetsov AV, Saks VA: Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria: determination of their molar stoichiometry. Biochem Biophys Res Commun 134: 359–366, 1986
Brooks SP, Suelter CH: Association of chicken mitochondrial creatine kiase with the inner mitochondrial membrane. Arch Biochem Biophys 253:122–132, 1987
Claycomb WC: Cardiac-muscle hypertrophy. Differentiation and growth of the heart cell during development. Biochem J 168:599–601, 1977
Claycomb WC: Biochemical aspects of cardiac muscle differentiation. J Biol Chem 250:3229–3235, 1975
Hopkins SF Jr, McCutcheon EP, Wekstein DR: Postnatal changes in rat ventricular function. Circ Res 32:685–691, 1973
Anversa P, Olivetti G, Bracchi P-G, Loud AV: Postnatal development of the M-band in rat cardiac myofibrils. Circ Res 48:561–568, 1981
Inversen LL, DeChamplain J, Glowinski J, Axelrod J: Uptake, storage and metabolism of norepinephrine in tissues of the developing rat. J Pharmacol Exp Ther 157:509–516, 1967
Claycomb WC: Biochemical aspects of cardiac muscle differentiation. J Biol Chem 251:6082–6089, 1976
Klein SC, Haas RC, Perryman MB, Billadello JJ, Strauss AW: Regulatory analysis and structural characterization of the human sarcomeric mitochondrial creatine kinase gene. J Biol Chem 266: 18058–18065, 1991
Smeitink J, Ruitenbeek W, van Lith T, Sengers R, Trijbels F, Wevers R, Sperl W, de Graaf R: Maturation of mitochondrial and other isoenzymes of creatine kinase in skeletal muscle of pretern born infants. Ann Clin Biochem 29:302–306, 1992
Friedman DL, Perryman MB: Compartmentation of multiple forms of creatine kinase in the distal nephron of the rat kidney. J Biol Chem 266:22404–22410, 1991
Webster KA, Gunning P, Hardeman E, Wallace DC, Kedes L: Coordinate reciprocal trends in glycolytic and mitochondrial transcript accumulations during thein vitro differentiation of human myoblasts. J Cell Physiol 142:566–573, 1990
Spizz G, Roman R, Strauss A, Olson EN: Serum and fibroblast growth factor inhibit myogenic differentiation through a mechanism dependent on protein synthesis and independent of cell proliferation. J Biol Chem 261:9483–9488, 1986
Trask RV, Strauss AW, Billadello JJ: Developmental regulation and tissue-specific expression of the human muscle creatine kinase gene. J Biol Chem 263:17142–17149, 1988
Lanson NA Jr, Glembotski CC, Steinhelper ME, Field LJ, Claycomb WC: Gene expression and atrial natriuretic factor processing and secretion in cultured AT-1 cardiac myocytes. Circulation 85:1835–1841, 1992
Su C-Y, Payne M, Strauss AW, Dillmann WH: Selective reduction of creatine kinase subunit mRNAs in striated muscle of diabetic rats. Am J Physiol 263 (Endocrinol Metab 26): E310–316, 1992
Lewis W, Papoian T, Gonzalez B, Louie H, Kelly DP, Payne RM, Grody WW: Mitochondrial ultrastructural and molecular changes induced by Zidovudine in rat hearts. Laboratory Investigation 65: 228–236, 1991
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Payne, R.M., Strauss, A.W. Expression of the mitochondrial creatine kinase genes. Mol Cell Biochem 133, 235–243 (1994). https://doi.org/10.1007/BF01267957
Issue Date:
DOI: https://doi.org/10.1007/BF01267957