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Trypanosoma cruzi Letm1 is involved in mitochondrial Ca 2+ transport, and is essential for replication, differentiation, and host cell invasion
Author(s) -
dos Santos Guilherme Rodrigo RM,
Rezende Leite Ana Catarina,
Lander Noelia,
Chiurillo Miguel Angel,
Vercesi Aníbal Eugênio,
Docampo Roberto
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202100120rr
Subject(s) - gene knockdown , microbiology and biotechnology , inner mitochondrial membrane , biology , mitochondrion , trypanosoma cruzi , bioenergetics , viability assay , intracellular , cell , biochemistry , apoptosis , parasite hosting , world wide web , computer science
Leucine zipper‐EF‐hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca 2+ and K + homeostasis in mammalian cells. Here, we demonstrate that the Letm1 orthologue of Trypanosoma cruzi , the etiologic agent of Chagas disease, is important for mitochondrial Ca 2+ uptake and release. The results show that both mitochondrial Ca 2+ influx and efflux are reduced in TcLetm1 knockdown ( TcLetm1 ‐KD) cells and increased in TcLetm1 overexpressing cells, without alterations in the mitochondrial membrane potential. Remarkably, TcLetm1 knockdown or overexpression increases or does not affect mitochondrial Ca 2+ levels in epimastigotes, respectively. TcLetm1 ‐KD epimastigotes have reduced growth, and both overexpression and knockdown of TcLetm1 cause a defect in metacyclogenesis. TcLetm1 ‐KD also affected mitochondrial bioenergetics. Invasion of host cells by TcLetm1 ‐KD trypomastigotes and their intracellular replication is greatly impaired. Taken together, our findings indicate that TcLetm1 is important for Ca 2+ homeostasis and cell viability in T cruzi .