Mitochondrial Ca2+ dynamics differ between the left and right ventricles in murine and porcine hearts

Abstract

Despite their differences in metabolism, mechanics, and developmental origin, the right ventricle (RV) is often assumed to function similarly to the left ventricle (LV). Specifically, though Ca 2+ transport into mitochondria is well established to play a crucial role in matching cardiac energy production to demand, little is known regarding whether mitochondrial Ca 2+ (mtCa 2+ ) handling is distinct in the RV and LV. Our objective was to test the hypothesis that the regulation of mtCa 2+ differs in the RV and LV. By isolating mitochondria from RV and LV free wall tissues from wild-type mice and healthy pigs, we compared several parameters indicative of Ca 2+ -regulated mitochondrial function. Basal mtCa 2+ levels were higher in RV mitochondria than in LV mitochondria. When successive boluses of Ca 2+ were administered to isolated mitochondria, RV mitochondria took up fewer Ca 2+ boluses, showing lower Ca 2+ retention capacity. RV mitochondria displayed relatively more protein carbonylation, suggesting oxidative stress. Interestingly, ATP production rate was higher in RV mitochondria relative to LV mitochondria; however, only LV mitochondria exhibited an increase in ATP production rate in the presence of Ca 2+ . We also compared the protein expression of the subunits of the mitochondrial Ca 2+ uniporter complex (MCUC) and the mitochondrial Na+/Ca 2+ exchanger (NCLX) and found that levels of the MCUC subunit Essential MCU Regulator (EMRE) and NCLX were higher in the LV than the RV, potentially facilitating more dynamic Ca 2+ transport in and out of LV mitochondria. Collectively, these data suggest that mtCa 2+ is calibrated to higher but more static levels in the RV, whereas in the LV basal mtCa 2+ is lower to ensure dynamic range for physiological stimuli to increase mitochondrial bioenergetics, corresponding to the larger changes in workload experienced by the LV. This study was supported by the National Institutes of Health (1K22HL137901 to Julia C. Liu) and by the Department of Integrative Biology and Physiology (to Jae Hwi Sung). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.