Figure 4.

HIF-1α is required for glycolytic switch after T. cruzi infection. (A) Two iPSC-CMs lines carrying HIF-1α^Δ301/-(compound inframe deletion of amino acid 301 and a null allele) or HIF-1α^Δ301-305/+ (a heterozygous inframe deletion of amino acids 301- 305) have lower infection and replicate rates compared to WT cells. (B) HIF-1α^Δ301/- iPSC-CMs did not activate proton efflux, an indicator of glycolytic activation. (C) Extracellular metabolic flux analyses demonstrated lower mitochondrial respiratory activity (oxygen consumption rate; OCR) in HIF-1α^Δ301/- iPSC-CMs at 48 hpi compared to WT. (D) HIF-1α^Δ301/- iPSC-CMs were unresponsive to LPS-priming. Data reflects six (A, B) and three (C, D) independent replicates for each experiment. Statistical analyses used ANOVA test with Bonferroni correction and p-value<0.05 was considered significant.