Control of energy production in the heart: a new function for fatty acid binding protein

Abstract

The quantitative subcellular distribution of the fatty acid binding protein (FABP) in heart muscle is reported for the first time. A gradient-like distribution according to the following pattern was observed: 6.96 mg X mL-1 on the myofibrils, 2.77 mg X mL-1 in the spaces surrounding the mitochondria, and 2.21 mg X mL-1 in the mitochondria. This heterogeneous distribution suggests that the local in vivo concentration of FABP might fluctuate as a function of time. The consequences of these possible fluctuations, particularly in the mitochondrial vicinity, were analyzed in an in vitro system containing a fixed concentration of cardiac mitochondria and stearic acid but variable concentrations of FABP. Competition for the fatty acid was observed between the mitochondrial membranes and the binding sites on the protein. Maximal binding of fatty acid to FABP was detected in the range of FABP concentration between 1 and 3 mg X mL-1. Remarkably, in this concentration range, two emerging peaks of beta-oxidative activity were also detected. As a major conclusion, it appears that the fatty acid pool, bound to FABP, is the source of fatty acid providing the beta-oxidative system with substrate. The mechanism of fatty acid transfer from this pool toward the beta-oxidative system remains an open question. However, it is suggested that a gradient-like distribution of FABP in the mitochondrial vicinity leads to the coexistence of multispecies of the protein by self-aggregation. Only two of these species seem to be involved in this fatty acid transfer. As a consequence, a strong modulation of fatty acid beta-oxidation rate is observed in isolated mitochondria when the concentrations of these two species are allowed to fluctuate. In conclusion, this unique cardiac fatty acid carrier, via its self-aggregation capacity and its in vivo gradient-like distribution, may act as a powerful effector in the regulation of heart energy.