Lactate Production Can Function to Increase Cell Iron Concentration

Presenter: Caroline Ghio

Research Category: Health Sciences
College: College of Engineering
Major(s): Chemical Engineering
Graduation Date: 2021

Iron is an essential micronutrient required by every cell. Under conditions of limited availability, plants and microbials evolved mechanisms to acquire iron, including a reprogramming of carbon metabolism with the activity of several enzymes involved in the Krebs cycle and glycolytic pathway. It was postulated that human cells similarly employ low molecular weight organic acids to import iron. My earlier findings showed that lactate increases iron import by intestinal Caco-2 cells (human epithelial colorectal adenocarcinoma cells) and increased iron availability is reflected by elevated cell ferritin following incubation with organic acids. Data also showed that co-incubation of metabolic intermediates/products of glycolysis and the Krebs Cycle with ferric ammonium citrate (FAC) results in higher concentrations of iron import by Caco-2 cells. Additionally, incubations of Caco-2 cells with both iron and organic acid results in greater concentrations of the iron storage protein ferritin. To test for additional associations, two additional objectives were developed: (1) Demonstrate the impact of iron on cellular lactate by varying concentrations of FAC to Caco-2 cells and collecting supernatant and cells to test for the presence of lactate dehydrogenase (LDH), an enzyme that plays a role in cellular respiration. (2) Observe the effect of iron on Caco-2 cells by performing RT-PCR on cells treated with FAC. Experiments showed that cell exposure to FAC decreased HIF-_ mRNA/_-Actin mRNA and LDH mRNA/_-Actin mRNA. Incubations with FAC significantly decreased concentrations of LDH. An understanding of these mechanisms may provide insight into diseases such as lactic acidosis, asthma, and cancer.