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Trypanosoma cruzi Letm1 is involved in mitochondrial Ca²⁺ transport, and is essential for replication, differentiation, and host cell invasion.

ABSTRACT: Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca²⁺ 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 Ca²⁺ uptake and release. The results show that both mitochondrial Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ homeostasis and cell viability in T cruzi.

SUBMITTER: Dos Santos GRR

PROVIDER: S-EPMC10437107 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Trypanosoma cruzi Letm1 is involved in mitochondrial Ca2+ transport, and is essential for replication, differentiation, and host cell invasion.

Dos Santos Guilherme Rodrigo Rm GRR Rezende Leite Ana Catarina AC Lander Noelia N Chiurillo Miguel Angel MA Vercesi Aníbal Eugênio AE Docampo Roberto R

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20210701 7

Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca2+ 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 Ca2+ uptake and release. The results show that both mitochondrial Ca2+ influx and efflux are reduced in TcLetm1 knockdown (TcLetm1-KD) cells and increase ...[more]

PMID: 34085343

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Dataset Information

Trypanosoma cruzi Letm1 is involved in mitochondrial Ca²⁺ transport, and is essential for replication, differentiation, and host cell invasion.

Publications

Trypanosoma cruzi Letm1 is involved in mitochondrial Ca<sup>2+</sup> transport, and is essential for replication, differentiation, and host cell invasion.

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