A computational study of the role of mitochondrial organization on cardiac bioenergetics.

All cells in the body have a specific shape and internal organization which is specific to that cell's function. Heart cells are rod-shaped, and contain arrays of contractile protines (myofibrils) and mitochondria (organelles that produce energy) that are aligned along the length of the rod. This arrangement is presumed to allow the cell to generate maximal contractile force for each heartbeat and for energy metabolites to be readily available to generate this force. Heart disease phenotypes, such as diabetic cardiomyopathy and heart failure, exhibit altered organization of mitochondria. However, physiological and computational studies have predominantly investigated the effect of the biochemical changes that accompany the disease alone, such as reduced rates of ATP production by mitochondria. We present a modeling study that examines the effect of mitochondrial organization on energy metabolite distribution during the heartbeat. A 2D micrograph of the cell cross-section was selected from a 3D image stack of structural data of a cardiac cell. The image was used to generate a 2D finite element model, on which mitochondrial oxidative phosphorylation and energy metabolite diffusion was modelled. Results illustrate that mitochondrial density can induce heterogeneity in the distribution of metabolites across the cell area. We discuss the implications of these findings and avenues for future, more indepth studies.