Glucokinase regulatory protein is associated with mitochondria in hepatocytes.
The association of glucokinase with liver mitochondria has been reported [Danial et al. (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424, 952-956]. We confirmed association of glucokinase immunoreactivity with rat liver mitochondria using Percoll gradient centrifugation and demonstrated its association with the 68 kDa regulatory protein (GKRP) but not with the binding protein phosphofructokinase-2/fructose bisphosphatase-2. Substrates and glucagon induced adaptive changes in the mitochondrial glucokinase/GKRP ratio suggesting a regulatory role for GKRP. Combined with previous observations that GKRP overexpression partially inhibits glycolysis [de la Iglesia et al. (2000) The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J. Biol. Chem. 275, 10597-10603] these findings suggest that there may be distinct glycolytic pools of glucokinase.
School of Clinical Medical Sciences-Diabetes, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK.
Catherine
C
Arden
Simone
S
Baltrusch
Loranne
L
Agius
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005941:Glucokinase / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity
D002352:Carrier Proteins; D005636:Fructosephosphates; C080906:glucokinase regulatory protein; C032284:fructose-1-phosphate; D005934:Glucagon; D006593:Hexokinase; D025481:Phosphofructokinase-2; D005941:Glucokinase; D006597:Fructose-Bisphosphatase