MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca 2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease and belongs to the early-branching eukaryotic supergroup Excavata. Its mitochondrial calcium uniporter (MCU) subunit shares similarity with the animal ortholog that was important to discover its encoding gene. In animal cells, the MICU1 and MICU2 proteins act as Ca 2+ sensors and gatekeepers of the MCU, preventing Ca 2+ uptake under resting conditions and favoring it at high cytosolic Ca 2+ concentrations ([Ca 2+ ] cyt ). Using the CRISPR/Cas9 technique, we generated TcMICU1 and TcMICU2 knockout cell lines and showed that MICU1 and -2 do not act as gatekeepers at low [Ca 2+ ] cyt but are essential for normal growth, host cell invasion, and intracellular replication, revealing lineage-specific adaptations.