PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum

Rotmann, Alexander; Sánchez, Cecilia P.; Guiguemde, Armand; Rohrbach, Petra; Dave, Anurag; Bakouh, Naziha; Planelles, Gabrielle; Lanzer, Michael

doi:10.1111/j.1365-2958.2010.07187.x

Cited by 40 publications

(58 citation statements)

References 69 publications

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“…A Ca 2+ /H + antiporter (CAX) was localized to P. falciparum mitochondria and sensitivity to ruthenium red and ruthenium 360 suggested the authors the presence of a Ca 2+ uniporter in these mitochondria [48]. However, there is no molecular evidence for the presence of an MCU [47] and the inhibitors might have had off site effects.…”

Section: Ca2+ Release and Leakage From Intracellular Sourcesmentioning

confidence: 99%

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

2015

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Apicomplexan parasites have complex life cycles, frequently split between different hosts and reliant on rapid responses as the parasites react to changing environmental conditions. Calcium ion (Ca2+) signaling is consequently essential for the cellular and developmental changes that support apicomplexan parasitism. Apicomplexan genomes reveal a rich repertoire of genes involved in calcium signaling, although many of the genes responsible for observed physiological changes remain unknown. There is evidence, for example, for the presence of a nifedipine-sensitive calcium entry mechanism in Toxoplasma, but the molecular components involved in Ca2+ entry in both Toxoplasma and Plasmodium, have not been identified. The major calcium stores are the endoplasmic reticulum (ER), the acidocalcisomes, and the plant-like vacuole in Toxoplasma, or the food vacuole in Plasmodium spp. Pharmacological evidence suggests that Ca2+ release from intracellular stores may be mediated by inositol 1,4,5-trisphosphate (IP3) or cyclic ADP ribose (cADPR) although there is no molecular evidence for the presence of receptors for these second messengers in the parasites. Several Ca2+-ATPases are present in apicomplexans and a putative mitochondrial Ca2+/H+ exchanger has been identified. Apicomplexan genomes contain numerous genes encoding Ca2+-binding proteins, with the notable expansion of calcium-dependent protein kinases (CDPKs), whose study has revealed novel roles in gliding motility, microneme secretion, host cell invasion and egress, and parasite differentiation. Microneme secretion has also been shown to depend on the C2 domain containing protein DOC2 in both Plasmodium spp. and Toxoplasma, providing further evidence for the complex transduction of Ca2+ signals in these organisms. The characterization of these pathways could lead to the discovery of novel drug targets and to a better understanding of the role of Ca2+ in these parasites.

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Section: Ca2+ Release and Leakage From Intracellular Sourcesmentioning

confidence: 99%

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

2015

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“…CAX from Plasmodium falciparum was suggested to be mitochondrial (Rotmann et al . 2010), while CAX from the related Plasmodium berghei was observed at an unknown endomembrane, possibly a secretory pathway location (Guttery et al . 2013), indicating that CAXs with very different subcellular locations in some species may exhibit very different physiological functions.…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

“…In contrast, it was suggested that PfCAX functions in Ca 2+ efflux from the inner mitochondrial matrix (Rotmann et al . 2010), a function performed by a CCX‐type Na + /Ca 2+ exchanger in animals (Palty et al . 2010), but by a less clear mechanism in plants (Wagner et al .…”

Section: Non‐plant Caxs – Lessons To Be Learned?mentioning

confidence: 99%

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

2016

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Cation/proton exchangers (CAXs) are a class of secondary energised ion transporter that are being implicated in an increasing range of cellular and physiological functions. CAXs are primarily Ca2+ efflux transporters that mediate the sequestration of Ca2+ from the cytosol, usually into the vacuole. Some CAX isoforms have broad substrate specificity, providing the ability to transport trace metal ions such as Mn2+ and Cd2+, as well as Ca2+. In recent years, genomic analyses have begun to uncover the expansion of CAXs within the green lineage and their presence within non‐plant species. Although there appears to be significant conservation in tertiary structure of CAX proteins, there is diversity in function of CAXs between species and individual isoforms. For example, in halophytic plants, CAXs have been recruited to play a role in salt tolerance, while in metal hyperaccumulator plants CAXs are implicated in cadmium transport and tolerance. CAX proteins are involved in various abiotic stress response pathways, in some cases as a modulator of cytosolic Ca2+ signalling, but in some situations there is evidence of CAXs acting as a pH regulator. The metal transport and abiotic stress tolerance functions of CAXs make them attractive targets for biotechnology, whether to provide mineral nutrient biofortification or toxic metal bioremediation. The study of non‐plant CAXs may also provide insight into both conserved and novel transport mechanisms and functions.

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“…But it is difficult to characterize the components of Ca 2+ -dependent signaling due to the lack of homology of effector molecules between Plasmodium and higher eukaryotes (83). Some effectors like Ca 2+ transporters, Pf CHA (PF3D7_0603500), similar to Ca 2+ /H + exchanger (84), P. falciparum sarco-endoplasmic reticulum calcium ATPase (SERCA-type ATPase), Pf ATP6 (PF3D7_0106300), and Pf ATP4 (85) have been identified, but their functions need to be investigated.…”

Section: Ca2+ Signalingmentioning

confidence: 99%

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

et al. 2017

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Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis. This review is intended to bring out the existing knowledge about the functions and components of the major signaling pathways such as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling, serving the various aspects of the parasitic asexual stage and highlighted the Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and molecular events in cytoadhesion, which elicit the host immune response. This discussion will facilitate a look over essential components for parasite survival and disease progression to be implemented in discovery of novel antimalarial drugs and vaccines.

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PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum

Cited by 40 publications

References 69 publications

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

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PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum

Cited by 40 publications

References 69 publications

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp

CAX‐ing a wide net: Cation/H+ transporters in metal remediation and abiotic stress signalling

Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

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CAX‐ing a wide net: Cation/H⁺ transporters in metal remediation and abiotic stress signalling