Abstract
Trypanosoma cruzi, the protozoan parasite that causes Chagas’ disease, exhibits peculiar biological features. Among them, the presence of a unique mitochondrion is remarkable. Even though the mitochondrial DNA constitutes up to 25% of total cellular DNA, the structure and functionality of the mitochondrion are dependent on the expression of the nuclear genome. As in other eukaryotes, specific peptide signals have been proposed to drive the mitochondrial localization of a subset of trypanosomatid proteins. However, there are mitochondrial proteins encoded in the nuclear genome that lack of a peptide signal. In other eukaryotes, alternative protein targeting to subcellular organelles via mRNA localization has also been recognized and specific mRNA localization towards the mitochondria has been described. With the aim of seeking for mitochondrial localization signals in T. cruzi, we developed a strategy to build a comprehensive database of nuclear genes encoding predicted mitochondrial proteins (MiNT) in the TriTryps (T. cruzi, T. brucei and L. major). We found that approximately 15% of their nuclear genome encodes mitochondrial products. In T. cruzi the MiNT database reaches 1438 genes and a conserved peptide signal, M(L/F) R (R/S) SS, named TryM-TaPe is found in 60% of these genes, suggesting that the canonical mRNA guidance mechanism is present. In addition, the search for compositional signals in the transcripts of T. cruzi MiNT genes produce a list, being worth to note a conserved non-translated element represented by the consensus sequence DARRVSG. Taking into account its reported interaction with the T. brucei TRRM3 protein which is enriched in the mitochondrial membrane fraction, we here suggest a putative zip code role for this element. Globally, here we provide an inventory of the mitochondrial proteins in T. cruzi and give evidence for the existence of both peptide and mRNA signals specific to nuclear encoded mitochondrial proteins.
Highlights
Trypanosoma cruzi (Kinetoplastidae, Trypanosomatidae) is the protozoan parasite that causes Chagas’ disease, known as American trypanosomiasis [1]
In the case of T. brucei, at least 1065 mitochondrial proteins encoded by the nuclear genome were predicted [15], we considered that the current number of genes in the MiNT database was still too low
Aiming to identify conserved signals among the nuclear genes encoding mitochondrial proteins in T. cruzi, we searched for the genes annotated as such in the TriTrypDB
Summary
Trypanosoma cruzi (Kinetoplastidae, Trypanosomatidae) is the protozoan parasite that causes Chagas’ disease, known as American trypanosomiasis [1]. The maxicircles (20–37 kb) are functionally equivalent to the mitochondrial DNA of other eukaryotes, and contain the genes encoding rRNAs (12S rRNA and 9S rRNA) and a reduced number of proteins (ND1; ND3;ND4; ND5; ND8; ND9; MURF1; MURF2; MURF5; COI; COII; COIII; Cyb; ATPase; CR3; CR4; RPS12) [3]. Their transcripts need to be extensively edited (uridine addition/ deletion) to solve features such as discontinuous open reading frames (ORFs), absence of essential elements for translation, i.e. initiation codons, or extensive modification to generate ORFs [4,5,6,7,8,9,10]. Proteomic analyses in T. brucei have enabled the identification of 1065 mitochondrial proteins from which only 18 are encoded in the mitochondrial genome [15]
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