The rapid and reversible association of phosphofructokinase with myocardial membranes during myocardial ischemia

Open Access
Publisher Website
Google Scholar
Abstract
Myocardial calcium‐independent phospholipase A2 (PLA2) activity is mediated by a 400 kDa catalytic complex comprised of a tetramer of phosphofructokinase (PFK) and a 40 kDa catalytic subunit [1,2]. During myocardial ischemia, calcium‐independent PLA2 activity rapidly and reversibly translocates from the cytosol to a membrane‐associated compartment where it has been implicated as a mediator of ischemic damage [3,4]. Herein we demonstrate that the majority of both PFK mass and activity is translocated from the cytosol to a membrane‐associated compartment prior to the onset of irreversible myocytic injury and that translocated PFK is catalytically inactive while membrane‐associated. Furthermore, reperfusion of ischemic myocardium, or treatment of membranes derived from ischemic myocardium with ATP results in the conversion of both PFK mass and activity from its membrane‐associated state to a soluble, catalytically‐competent form. Collectively, these studies demonstrate that the concomitant changes in glycolysis and phospholipid hydrolysis during early myocardial ischemia result, at least in part, from the translocation of a common regulatory polypeptide critical in both processes.