Muscle FBPase binds to cardiomyocyte mitochondria under glycogen synthase kinase-3 inhibition or elevation of cellular Ca2+ level

FEBS Lett. 2012 Jan 2;586(1):13-9. doi: 10.1016/j.febslet.2011.11.032. Epub 2011 Dec 7.

Abstract

A growing body of research suggests that fructose 1,6-bisphosphatase (FBPase) might be involved in regulation of cell mortality/survival. However, the precise role of FBPase in the process remains unknown. Here, we show for the first time that in HL-1 cardiomyocytes, inhibition of glycogen synthase kinase-3 results in translocation of FBPase to mitochondria. In vitro experiments demonstrate that FBPase reduces the rate of calcium-induced mitochondrial swelling, affects ATP synthesis and interacts with mitochondrial proteins involved in regulation of volume and energy homeostasis. We suggest that FBPase might be engaged in a regulation of cell survival by influencing mitochondrial function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Binding, Competitive
  • Calcium / metabolism*
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Fructose-Bisphosphatase / metabolism*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Indoles / pharmacology
  • Maleimides / pharmacology
  • Mice
  • Mitochondria, Heart / metabolism*
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Swelling / physiology
  • Myocardium / enzymology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Protein Transport
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Enzyme Inhibitors
  • Indoles
  • Maleimides
  • Mitochondrial Proteins
  • Recombinant Proteins
  • SB 216763
  • Adenosine Triphosphate
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Fructose-Bisphosphatase
  • Calcium