Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: The role of sarcomeric mitochondrial creatine kinase

被引:44
作者
Steeghs, K
Heerschap, A
deHaan, A
Ruitenbeek, W
Oerlemans, F
vanDeursen, J
Perryman, B
Pette, D
Bruckwilder, M
Koudijs, J
Jap, P
Wieringa, B
机构
[1] UNIV NIJMEGEN, FAC MED SCI, DEPT CELL BIOL & HISTOL, NL-6500 HB NIJMEGEN, NETHERLANDS
[2] UNIV NIJMEGEN, FAC MED SCI, DEPT DIAGNOST RADIOL, NL-6500 HB NIJMEGEN, NETHERLANDS
[3] VRIJE UNIV AMSTERDAM, DEPT MUSCLE & EXERCISE PHYSIOL, NL-1081 BT AMSTERDAM, NETHERLANDS
[4] UNIV NIJMEGEN, FAC MED SCI, DEPT PAEDIAT, NL-6500 HB NIJMEGEN, NETHERLANDS
[5] ST JUDE CHILDRENS RES HOSP, DEPT GENET, MEMPHIS, TN 38101 USA
[6] UNIV COLORADO, HLTH SCI CTR, DIV CARDIOL, DENVER, CO 80262 USA
[7] UNIV KONSTANZ, DEPT BIOL, D-7834 CONSTANCE, GERMANY
关键词
creatine kinase; mitochondria; gene targeting; energy homeostasis; muscle physiology; oxidative phosphorylation;
D O I
10.1016/S0165-0270(96)00124-0
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We have introduced a single knock-out mutation in the mitochondrial creatine kinase gene (ScCKmit) in the mouse germ line via targeted mutagenesis in mouse embryonic stem (ES) cells. Surprisingly, ScCKmit -/- muscles, unlike muscles of mice with a deficiency of cytosolic M-type creatine kinase (M-CK -/-; Van Deursen et al, (1993) Cell 74, 621-631), display no altered morphology, performance or oxidative phosphorylation capacity. Also, the levels of high energy phosphate metabolites were essentially unaltered in ScCKmit mutants, Our results challenge some of the present concepts about the strict coupling between CKmit function and aerobic respiration.
引用
收藏
页码:29 / 41
页数:13
相关论文
共 87 条
[81]   REVERSIBLE MM-CREATINE KINASE BINDING TO CARDIAC MYOFIBRILS [J].
VENTURACLAPIER, R ;
SAKS, VA ;
VASSORT, G ;
LAUER, C ;
ELIZAROVA, GV .
AMERICAN JOURNAL OF PHYSIOLOGY, 1987, 253 (03) :C444-C455
[82]   INTRACELLULAR COMPARTMENTATION, STRUCTURE AND FUNCTION OF CREATINE-KINASE ISOENZYMES IN TISSUES WITH HIGH AND FLUCTUATING ENERGY DEMANDS - THE PHOSPHOCREATINE CIRCUIT FOR CELLULAR-ENERGY HOMEOSTASIS [J].
WALLIMANN, T ;
WYSS, M ;
BRDICZKA, D ;
NICOLAY, K ;
EPPENBERGER, HM .
BIOCHEMICAL JOURNAL, 1992, 281 :21-40
[83]   INSITU COMPARTMENTATION OF CREATINE-KINASE IN INTACT SARCOMERIC MUSCLE - THE ACTOMYOSIN OVERLAP ZONE AS A MOLECULAR-SIEVE [J].
WEGMANN, G ;
ZANOLLA, E ;
EPPENBERGER, HM ;
WALLIMANN, T .
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, 1992, 13 (04) :420-435
[84]   MITOCHONDRIAL CREATINE-KINASE - A KEY ENZYME OF AEROBIC ENERGY-METABOLISM [J].
WYSS, M ;
SMEITINK, J ;
WEVERS, RA ;
WALLIMANN, T .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1102 (02) :119-166
[85]   FORMATION OF CREATINE-PHOSPHATE FROM CREATINE AND P-32-LABELED ATP BY ISOLATED RABBIT HEART-MITOCHONDRIA [J].
YANG, WCT ;
GEIGER, PJ ;
BESSMAN, SP ;
BORREBAEK, B .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1977, 76 (03) :882-887
[86]   ANALYSIS OF COMPARTMENTATION OF ATP IN SKELETAL AND CARDIAC-MUSCLE USING P-31 NUCLEAR-MAGNETIC-RESONANCE SATURATION TRANSFER [J].
ZAHLER, R ;
BITTL, JA ;
INGWALL, JS .
BIOPHYSICAL JOURNAL, 1987, 51 (06) :883-893
[87]   ADENYLATE KINASE-CATALYZED PHOSPHORYL TRANSFER COUPLES ATP UTILIZATION WITH ITS GENERATION BY GLYCOLYSIS IN INTACT MUSCLE [J].
ZELEZNIKAR, RJ ;
DZEJA, PP ;
GOLDBERG, ND .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (13) :7311-7319