The temperature dependence of platelet metabolism

Temperature plays a fundamental role in biology, influencing cellular function, affecting chemical reaction rates, molecular structures, and interactions. While the temperature dependence of many biochemical reactions is well defined in vitro, the effect of temperature on metabolic function at the network level is not well understood but remains an important challenge in optimizing the storage of cells and tissues at lower temperatures. Here, we have used time-course metabolomics data and systems biology approaches to characterize the effects of storage temperature on human platelets (PLTs) in platelet additive solution. We observed that changes to the metabolome with storage time do not simply scale with temperature but instead display complex temperature dependence, with only a small subset of metabolites following an Arrhenius-type. Investigation of PLT energy metabolism through integration with computational modeling revealed that oxidative metabolism is more sensitive to temperature changes than is glycolysis. The increased contribution of glycolysis to ATP turnover at lower temperature indicates a stronger glycolytic phenotype with decreasing storage temperature. More broadly, these results demonstrate that the temperature dependence of the PLT metabolic network is not uniform, suggesting that efforts to improve the health of stored PLTs could be targeted at specific pathways.\n\nStatement of SignificanceThe temperature dependence of cellular metabolism is difficult to study due to regulatory events that are activated upon deviation from the optimal temperature range. Platelets are blood components used in transfusion medicine but also serve as a model cell to study human energy metabolism in the absence of genetic regulation. We investigated changes in platelet metabolism at temperatures spanning from 4 {degrees}C-37 {degrees}C using a quantitative metabolic systems biology approach as opposed to assessing individual reactions. We found that energy producing metabolic pathways have different temperature sensitivities. The results define the metabolic response to temperature on the metabolic pathway level and are of importance for understanding the cryopreservation of human platelets and more complex human cells used in cellular therapy.