Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii

Salunke, Rahul; Mourier, Tobias; Banerjee, Manidipa; Pain, Arnab; Shanmugam, Dhanasekaran

doi:10.1371/journal.pbio.2006128

Cited by 51 publications

(63 citation statements)

References 81 publications

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“…During the revision of this manuscript, a similar set of proteins was identified as part of a proteomic analysis of the purified T. gondii ATP synthase complex ( Salunke et al, 2018 ). In addition to the novel subunits we described, the authors describe ten additional subunits, which our proteomic analysis identified, but we excluded on the basis of lack of conservation in either C. muris , P. falciparum , or C. velia ( Supplementary file 1 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of cryptic subunits from an apicomplexan ATP synthase

Huet

Rajendran

Dooren

et al. 2018

eLife

103

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The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

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Section: Discussionmentioning

confidence: 99%

Identification of cryptic subunits from an apicomplexan ATP synthase

Huet

Rajendran

Dooren

et al. 2018

eLife

103

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“…To further confirm its identity as complex IV, we performed mass spectrometry analysis of this band which confirmed the complex identity, through confirming the presence of all complex IV components (Table S5). Complex V assay was reported for T. gondii previously (Salunke et al, 2018) and we followed the same protocol here. To provide additional confirmation to the complex identity we used an antibody raised against a consensus sequence found in plant, algal and bacterial ATP-beta subunit of complex V, and which was shown to cross-react with ATP-beta from a variety of organisms including T. gondii (Huet et al, 2018;Seidi et al, 2018).…”

Section: A New Protocol For Evaluation Of Mitochondrial Translation Smentioning

confidence: 99%

“…For example, enriched mitochondria are used for the complex V enzymatic activity performed using native-PAGE technique (Fig. 6B; Salunke et al, 2018). The protocol we develop here for one of the most tractable apicomplexan parasites can be used to develop additional assays.…”

Section: A New Protocol To Follow Mitochondrial Translation In T Gondiimentioning

confidence: 99%

Identification of the Toxoplasma gondii mitochondrial ribosome, and characterisation of a protein essential for mitochondrial translation

Lacombe

Maclean

Ovciarikova

et al. 2019

Molecular Microbiology

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Summary Apicomplexan parasites cause diseases such as malaria and toxoplasmosis. The apicomplexan mitochondrion shows striking differences from common model organisms, including fundamental processes such as mitochondrial translation. Despite evidence that mitochondrial translation is essential for parasite survival, it is largely understudied. Progress has been restricted by the absence of functional assays to detect apicomplexan mitochondrial translation, a lack of knowledge of proteins involved in the process and the inability to identify and detect mitoribosomes. We report the localization of 12 new mitochondrial proteins, including 6 putative mitoribosomal proteins. We demonstrate the integration of three mitoribosomal proteins in macromolecular complexes, and provide evidence suggesting these are apicomplexan mitoribosomal subunits, detected here for the first time. Finally, a new analytical pipeline detected defects in mitochondrial translation upon depletion of the small subunit protein 35 (TgmS35), while other mitochondrial functions remain unaffected. Our work lays a foundation for the study of apicomplexan mitochondrial translation.

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“…Only those proteins required for the maintenance of its genome are fully transcribed and translated within the organelle 42 . Mitochondrial tRNAs, and ATP synthase subunits are known to be imported in T. gondii 55,62,63 . Noteworthy, a functional cox1 copy has been annotated in the T. gondii nuclear genome (TgME49_209260), and a homolog is present in the reference NcLiv genome (NCLIV_003650).…”

Section: Discussionmentioning

confidence: 99%

Reevaluation of theToxoplasma gondiiandNeospora caninumgenomes reveals misassembly, karyotype differences and chromosomal rearrangements

Berná

Marquez

Cabrera

et al. 2020

Preprint

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Neospora caninum primarily infects cattle causing abortions with an estimated impact of a billion dollars on worldwide economy, annually. However, the study of its biology has been unheeded by the established paradigm that it is virtually identical to its close relative, the widely studied human pathogen, Toxoplasma gondii. By revisiting the genome sequence, assembly and annotation using third generation sequencing technologies, here we show that the N. caninum genome was originally incorrectly assembled under the presumption of synteny with T. gondii. We show that major chromosomal rearrangements have occurred between these species. Importantly, we show that chromosomes originally annotated as ChrVIIb and VIII are indeed fused, reducing the karyotype of both N. caninum and T. gondii to 13 chromosomes. We reannotate the N. caninum genome, revealing over 500 new genes. We sequence and annotate the non-photosynthetic plastid and mitochondrial genomes, and show that while apicoplast genomes are virtually identical, high levels of gene fragmentation and reshuffling exists between species and strains. Our results correct assembly artifacts that are currently widely distributed in the genome database of N. caninum and T. gondii, but more importantly, highlight the mitochondria as a previously oversighted source of variability and pave the way for a change in the paradigm of synteny, encouraging rethinking the genome as basis of the comparative unique biology of these pathogens.

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Highly diverged novel subunit composition of apicomplexan F-type ATP synthase identified from Toxoplasma gondii

Cited by 51 publications

References 81 publications

Identification of cryptic subunits from an apicomplexan ATP synthase

Identification of cryptic subunits from an apicomplexan ATP synthase

Identification of the Toxoplasma gondii mitochondrial ribosome, and characterisation of a protein essential for mitochondrial translation

Reevaluation of theToxoplasma gondiiandNeospora caninumgenomes reveals misassembly, karyotype differences and chromosomal rearrangements

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