Mitochondrial hexokinase and cardioprotection of the intact heart.
The interaction of hexokinase with mitochondria has emerged as a powerful mechanism in protecting many cell types against cell death. However, the role of mitochondrial hexokinase (mitoHK) in cardiac ischemia-reperfusion injury has as of yet received little attention. In this review we examine whether increased binding of hexokinase to the mitochondrion is also an integral component of cardioprotective signalling. We discuss observations in cardiac mitochondrial activation that directed us to the hypothesis of hexokinase cellular redistribution with reversible, cardioprotective ischemia, summarize the data showing that many cardioprotective interventions, such as ischemic preconditioning, insulin, morphine and volatile anesthetics, increase mitochondrial hexokinase binding within the intact heart, and discuss similarities between mitochondrial hexokinase association and ischemic preconditioning. Although most data indicate that mitochondrial hexokinase may indeed be an integral part of cardioprotection, a definitive proof for a causal relation between the amount of mitoHK and cardiac ischemia-reperfusion injury in the intact heart is eagerly awaited. When such relationship is indeed observed, the association of hexokinase with mitochondria will offer an opportunity to develop new therapies to combat ischemic cardiac diseases.
Laboratory of Experimental Intensive Care & Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
C J
CJ
Zuurbier
K M A
KM
Smeele
O
O
Eerbeek
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000201:enzymology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000628:therapy; D009206:Myocardium / Q000201:enzymology*; D015398:Signal Transduction
D002316:Cardiotonic Agents; D006593:Hexokinase