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The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis

  • Antonia Blank ,

    Contributed equally to this work with: Antonia Blank, Solomon Ngwira

    Roles Writing – original draft, Writing – review & editing

    Affiliations Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America, Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, United States of America

    ⨯
  • Solomon Ngwira ,

    Contributed equally to this work with: Antonia Blank, Solomon Ngwira

    Roles Writing – original draft, Writing – review & editing

    Affiliations Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America, Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, United States of America

    ⨯
  • Manuel A. Fierro

    Roles Conceptualization, Funding acquisition, Supervision, Writing – original draft, Writing – review & editing

    fierroc@clemson.edu

    Affiliations Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America, Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina, United States of America

    ⨯

Abstract

As a eukaryote, Plasmodium, the causative agent of malaria, is reliant on its endoplasmic reticulum (ER) for survival. However, as a protozoan pathogen, Plasmodium has also adapted its ER to support its parasitic lifestyle. This Pearl focuses on the interplay between conserved ER functions in Plasmodium such as cell signaling, protein synthesis/secretion, lipid production, and cellular stress, and their contribution to parasite pathogenesis. We further summarize the current knowledge about the role of the ER in pathogenic processes such as motility, egress/invasion, host-cell remodeling, and transmission throughout the blood, liver, sexual, and mosquito stages. Collectively, we hope that discussing the Plasmodium ER as both a conserved cellular hub and a source of parasite-specific biology offers promising opportunities for antimalarial strategies.

Citation: Blank A, Ngwira S, Fierro MA (2026) The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis. PLoS Pathog 22(8): e1014539. https://doi.org/10.1371/journal.ppat.1014539

Editor: Tobias Spielmann, Bernhard-Nocht-Institute for Tropical Medicine, GERMANY

Published: August 25, 2026

Copyright: © 2026 Blank et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the National Institute of General Medical Sciences award P20GM146584. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The endoplasmic reticulum (ER) is a eukaryotic organelle that functions as a hub for protein synthesis/trafficking [1,2], calcium (Ca2+) signaling [3], and stress responses [4]. Understanding the role of the ER in adaptations like parasitism reveals new insights into anti-pathogen treatment. Towards this goal, this review will focus on the intracellular parasite Plasmodium, the causative agent of malaria. Plasmodium maintains conserved ER core functions present across other eukaryotes [5–7] including Ca2+ storage [8], glycosylation [9], protein quality control [10], and protein secretion [11]. We will discuss the known functions of the Plasmodium ER, their impact in parasite pathogenesis, and implications for antimalarial development.

The architecture of the ER across the Plasmodium life cycle

The ER is a dynamic organelle whose architecture is maintained by various proteins [12]. One ER-shaping protein called Yop1, which in other eukaryotes interacts with reticulons to organize ER tubules, is important for ER structure and virulence in P. berghei [13]. Other ER-shaping proteins have been identified bioinformatically [14], but their functional conservation across the life cycle remains to be studied. In contrast, the general architecture of the ER across its complex life cycle is well characterized.

Blood stages

Like other eukaryotes, the ER of Plasmodium wraps itself around the nucleus, producing a distinctive peri-nuclear pattern observed in the blood stages of P. falciparum [15 – 17] (Fig 1) and P. berghei [18]. This peri-nuclear pattern changes from a condensed form with some protrusions in the ring stages, to a larger form that contains several protrusions or condensed foci during the trophozoite stage [15–18] (Fig 1). These protrusions appear to contact organelles like the mitochondria [16] while expansion microscopy of condensed foci has revealed their composition to be compact ER cisternae [17]. Upon entering schizogony, the ER volume begins to extend throughout the cell body, and several interconnected ringlet patterns appear due to the newly synthesized nuclei that have divided in preparation for daughter-cell formation [15–18]. Once schizogony finishes, the ER ringlets sepBlood stagesarate and encapsulate each new daughter merozoite’s nucleus (Fig 1).

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Fig 1. The architecture of the ER during Plasmodium falciparum’s blood stages.

Representative images showing the structural development of the ER across the blood stages. The ER and nucleus were visualized by staining parasites with ER Tracker (red, Invitrogen) and Hoescht (blue, Invitrogen). Images were taken under the same conditions. Scale bar: 5 µm for all images.

https://doi.org/10.1371/journal.ppat.1014539.g001

Sexual stages

Sexual stages, known as gametocytes, are a subset group of the blood stage and have a unique morphology compared to their other blood stage counterparts. Using electron microscopy (EM) techniques to study gametocyte organellar ultrastructure, Evers and colleagues [19] demonstrated that the ER of female gametocytes in P. falciparum occupies a larger volume compared to male gametes or immature gametocytes. The authors attribute this discrepancy to increased protein synthesis in female gametocytes compared to their male counterparts. Moreover, their data suggests that the ER of both sexes contains several contact sites including the Golgi, mitochondria, the Inner Membrane Complex, and plasma membrane (PPM).

Liver stages

During the liver stages, the ER displays a similar yet more dynamic structure compared to its blood stage counterparts which is partly due to the dramatic asexual expansion occurring in hepatocytes [20]. Using confocal microscopy, sub-compartmentalization in the ER of P. berghei was observed by overlapping yet distinct ER distributions of the soluble, ER chaperone BiP and the ER membrane protein Sec61β [18]. Like the blood stages, large aggregate structures were also visible throughout liver stage schizonts which were determined by EM to be complexed ER tubule bundles [18]. The liver stage ER was also proven to be a single, interconnected organelle throughout the cycle that segregates into separate organelles at the very end of the liver stages, coinciding with newly formed merozoites. Interestingly, like gametocytes, the ER of liver stages also contains regions where ER-PPM contact sites can be observed by EM [18].

Mosquito stages

Less is known about the role of the ER in the mosquito stages due to the difficulty of acquiring these forms in the laboratory. However, basic structural studies using confocal microscopy demonstrated that the ER of P. berghei ookinetes, the stage emerging after gamete fertilization, surrounds the nucleus and extends across the body of the parasite similar to female gametocytes [18]. As the parasites transition into the oocyst stage, the ER begins to structurally mimic that of liver stages with large ER accumulations observed throughout the developing oocysts, culminating in perinuclear ER forms surrounding the nucleus of individual sporozoites. The similarities between liver schizonts and oocysts are likely due to the hyperactive replication that occurs in these stages. Once sporozoites develop, the ER extends across the whole body of the parasite similar to ookinetes [18].

Function of ER Ca2+ in parasite biology

The Plasmodium ER is thought to be the primary compartment for Ca2+ signaling/storage. As such, it contains mechanisms for replenishing ER Ca2+ [21] and ER Ca2+ buffering [22]. However, Plasmodium lacks an annotated IP3/Ryanodine receptor for signal-dependent ER Ca2+ release [21]. One candidate, ICM1, has been shown to be important for this process during parasite egress/invasion in P. falciparum [23], yet its localization/function across other blood stages remains unknown. Similarly, the ER Ca2+-binding protein ERC plays a role in parasite egress from red blood cells (RBCs) [8]. Indeed, most of what is known about the role of Ca2+ in Plasmodium spp. is generally related to entering [24] and exiting [25] RBCs, male gamete activation [21], and motility [21]. These events are coordinated by signal-based release of apical organelles and all work in conjunction with other secondary messengers like cGMP, cAMP, and xanthurenic acid. More importantly, disruption of Ca2+-related events is lethal to parasites showing that identification of all the players involved in ER Ca2+ release/storage provides a rich source of potential antimalarial targets.

Plasmodium’s innovative secretory pathway

Plasmodium contains conserved mechanisms for chaperone-mediated protein trafficking [22] and retention of ER proteins [26]. These trafficked proteins are then targeted to either internal (i.e., secretory organelles, apicoplast, etc.) or external compartments (i.e., Parasitophorous Vacuole, RBC) [22] and ER protein trafficking mechanisms are a target of emerging antimalarials [27,28]. One innovative trafficking mechanism in the parasite is the process for sending cargo destined to the apicoplast, a relict plastid acquired from past endosymbiotic events, by duplication of ERAD machinery to help import apicoplast-destined cargo transcribed from the nucleus [29]. Another example is the export of proteins to the RBC. In Plasmodium, most exported proteins contain a N-terminal Plasmodium Export Element (PEXEL) motif which is a proteolytic cleavage site required for export of this class of proteins [30,31]. Upon ER entry, the PEXEL is cleaved by a distinct Sec61-associated complex containing the aspartic protease Plasmepsin V (PMV), replacing the role of Signal Peptidase [32]. While the reason for a separate translocon is unclear, it likely arose to alleviate trafficking of exported cargo through the canonical Sec6-Signal Peptidase complex by deviating it to distinct machinery [33]. More importantly, PMV is essential for parasite viability and the target of several compounds [34,35].

The role of the ER in protein modifications

The ER is a well-established site for post-translational modifications of nascent proteins. One of these modifications is the addition of disulfide bonds, which form in the ER’s reducing environment. This is carried out by ER-resident Protein Disulfide Isomerases (PDIs) which, in P. falciparum, are encoded by four PDIs [36]. Of these four, PDI8 is the only one confirmed to be essential for parasite growth and works with PDI11, PfJ2, and BiP to properly fold proteins in the ER lumen [36]. Another notable modification in the parasites is protein glycosylation which appears to only occur in the ER in contrast to model eukaryotes that additionally use the Golgi for this process [9,37,38]. The most abundant glycan in Plasmodium spp is glycophosphatidylinositol (GPI), an essential component of GPI anchors [37] and used by invasion-related proteins like MSP1 [9] and CSP [39]. Moreover, evidence of O-fucosylation, and C-mannosylation have also been found in the parasites [9, 37, 38] which play a stabilizing role for CSP and TRAP during mosquito and liver stages [9, 37, 38]. While some studies report the presence of N-glycosylation [38], it’s not clear if any proteins are extensively N-glycosylated in Plasmodium. In general, glycosylation in Plasmodium appears to function in stage transmission [40,41], providing an attractive antimalarial strategy.

Lipid synthesis

Synthesis of lipids required for membrane biogenesis and energy occurs in the eukaryotic smooth ER [42]. Despite the need to scavenge precursor molecules, P. falciparum contains the essential ER machinery required for production of these necessary lipids [43]. Not surprisingly, the ER has multiple contact sites with various organelles [16, 19] and the PPM [18,19] to facilitate the transfer of lipids as previously demonstrated for PfPSS in the mitochondria [16] and PfVAP/PfVPS13L1 in the inner membrane complex (IMC) [44]. The ER is also a hub for lipid droplet (LD) formation which are crucial for lipid homeostasis. Studies in P. falciparum show that LDs are associated with the ER and required for parasite survival [45], yet the molecular players involved in this process are yet to be determined. Lastly, phosphatidylcholine produced by a host-derived precursor plays a crucial role in sexual differentiation showing another potential avenue for anti-transmission strategies [46].

ER stress pathways and drug resistance

The ER is a major site of stress surveillance and, thus, contains several mechanisms to deal with cellular stress [4,47,48]. Of the three ER-related stress pathways found in eukaryotes (IRE1-mediated, PERK-mediated, ATF6-mediated), Plasmodium is only capable of global translational arrest via the PERK pathway [18,28]. Translational arrest is a key feature in the progression of P. falciparum’s lifecycle as eIF2α phosphorylation can be identified in terminal stages such as the schizont stage in RBCs [49] or in sporozoites [50]. Interestingly, activation of this pathway has been shown to be induced in the presence of the frontline antimalarial, artemisinin [49], a process modified in artemisinin-resistance parasites [51]. Thus, inactivation of this pathway has important implications to counter parasite recrudescence after artemisinin treatment to improve its efficacy in resistant parasites.

Conclusion

While generally conserved ER features exist in Plasmodium, these parasites have tweaked their use to uniquely fit their parasitic lifestyle. Thus, with the present state of antimalarial strategies, focus on the Plasmodium ER can provide novel points of attack against this deadly parasite. Indeed, recent proteomic studies have highlighted conserved mechanisms as well as novel ER-associated proteins whose functional characterization would be of interest to the wide community [44,52,53]. Moreover, by taking advantage of current advances in genetics, microscopy, and proteomics, future Plasmodium studies should continue characterizing: (1) the mechanism for ER structural maintenance; (2) how Ca2+ is released from the ER; (3) sites of ER entry/exit; (4) all the molecular players involved in glycosylation; and (5) the process of LD formation. We hope this review re-stimulates attention to this fascinating organelle.

Acknowledgments

We thank Dr. Gary Ward and Dr. Vasant Muralidharan for helpful comments regarding the manuscript.

References

  1. 1. Barlowe CK, Miller EA. Secretory protein biogenesis and traffic in the early secretory pathway. Genetics. 2013;193(2):383–410. pmid:23396477
  2. 2. Itskanov S, Park E. Mechanism of protein translocation by the Sec61 translocon complex. Cold Spring Harb Perspect Biol. 2023;15(1):a041250. pmid:35940906
  3. 3. Daverkausen-Fischer L, Pröls F. Regulation of calcium homeostasis and flux between the endoplasmic reticulum and the cytosol. J Biol Chem. 2022;298(7):102061. pmid:35609712
  4. 4. Chen X, Shi C, He M, Xiong S, Xia X. Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct Target Ther. 2023;8(1):352. pmid:37709773
  5. 5. Klinger CM, Klute MJ, Dacks JB. Comparative genomic analysis of multi-subunit tethering complexes demonstrates an ancient pan-eukaryotic complement and sculpting in Apicomplexa. PLoS One. 2013;8(9):e76278. pmid:24086721
  6. 6. Woo YH, Ansari H, Otto TD, Klinger CM, Kolisko M, Michálek J, et al. Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites. Elife. 2015;4:e06974. pmid:26175406
  7. 7. Klinger CM, Ramirez-Macias I, Herman EK, Turkewitz AP, Field MC, Dacks JB. Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology. Mol Biochem Parasitol. 2016;209(1–2):88–103. pmid:27444378
  8. 8. Fierro MA, et al. An endoplasmic reticulum CREC family protein regulates the egress proteolytic cascade in malaria parasites. mBio. 2020;11.
  9. 9. Gowda DC, Miller LH. Glycosylation in malaria parasites: what do we know?. Trends Parasitol. 2024;40(2):131–46. pmid:38262838
  10. 10. Chaubey S, Grover M, Tatu U. Endoplasmic reticulum stress triggers gametocytogenesis in the malaria parasite. J Biol Chem. 2014;289(24):16662–74. pmid:24755215
  11. 11. Mayer DCG. Protein sorting in Plasmodium falciparum. Life (Basel). 2021;11(9):937. pmid:34575086
  12. 12. Obara CJ, Moore AS, Lippincott-Schwartz J. Structural diversity within the endoplasmic reticulum-from the microscale to the nanoscale. Cold Spring Harb Perspect Biol. 2023;15(6):a041259. pmid:36123032
  13. 13. Shi X, Hai L, Govindasamy K, Gao J, Coppens I, Hu J, et al. A Plasmodium homolog of ER tubule-forming proteins is required for parasite virulence. Mol Microbiol. 2020;114(3):454–67. pmid:32432369
  14. 14. Sun S, Lv L, Yao Z, Bhanot P, Hu J, Wang Q. Identification of endoplasmic reticulum-shaping proteins in Plasmodium parasites. Protein Cell. 2016;7(8):615–20. pmid:27484902
  15. 15. van Dooren GG, Marti M, Tonkin CJ, Stimmler LM, Cowman AF, McFadden GI. Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol Microbiol. 2005;57(2):405–19. pmid:15978074
  16. 16. Anwar MO, Islam MM, Thakur V, Kaur I, Mohmmed A. Defining ER-mitochondria contact dynamics in Plasmodium falciparum by targeting component of phospholipid synthesis pathway, phosphatidylserine synthase (PfPSS). Mitochondrion. 2022;65:124–38. pmid:35623558
  17. 17. Liffner B, Cepeda Diaz AK, Blauwkamp J, Anaguano D, Frolich S, Muralidharan V, et al. Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy. Elife. 2023;12:RP88088. pmid:38108809
  18. 18. Kaiser G, De Niz M, Zuber B, Burda P-C, Kornmann B, Heussler VT, et al. High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum. Mol Microbiol. 2016;102(5):775–91. pmid:27566438
  19. 19. Evers F, Roverts R, Boshoven C, Kea-Te Lindert M, Verhoef JMJ, Sommerdijk N, et al. Comparative 3D ultrastructure of Plasmodium falciparum gametocytes. Nat Commun. 2025;16(1):69. pmid:39747010
  20. 20. Roques M, Bindschedler A, Beyeler R, Heussler VT. Same, same but different: exploring Plasmodium cell division during liver stage development. PLoS Pathog. 2023;19(3):e1011210. pmid:36996035
  21. 21. de Oliveira LS, Alborghetti MR, Carneiro RG, Bastos IMD, Amino R, Grellier P, et al. Calcium in the backstage of malaria parasite biology. Front Cell Infect Microbiol. 2021;11:708834. pmid:34395314
  22. 22. Florentin A, Cobb DW, Kudyba HM, Muralidharan V. Directing traffic: chaperone-mediated protein transport in malaria parasites. Cell Microbiol. 2020;22(7):e13215. pmid:32388921
  23. 23. Balestra AC, Koussis K, Klages N, Howell SA, Flynn HR, Bantscheff M, et al. Ca2+ signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG. Sci Adv. 2021;7(13):eabe5396. pmid:33762339
  24. 24. Alam N, Farrell B, Jamwal A, Higgins MK. Erythrocyte invasion in malaria: from molecular mechanisms to rational vaccines. Nat Rev Microbiol. 2026;24(2):97–110. pmid:40954307
  25. 25. Dvorin JD, Goldberg DE. Plasmodium egress across the parasite life cycle. Annu Rev Microbiol. 2022;76:67–90.
  26. 26. Fierro MA, Hussain T, Campin LJ, Beck JR. Knock-sideways by inducible ER retrieval enables a unique approach for studying Plasmodium-secreted proteins. Proc Natl Acad Sci U S A. 2023;120(33):e2308676120. pmid:37552754
  27. 27. LaMonte GM, Rocamora F, Marapana DS, Gnädig NF, Ottilie S, Luth MR, et al. Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway. Nat Commun. 2020;11(1):1780. pmid:32286267
  28. 28. Harbut MB, et al. Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design. Proc Natl Acad Sci U S A. 2012;109:21486–91.
  29. 29. Agrawal S, Chung D-WD, Ponts N, van Dooren GG, Prudhomme J, Brooks CF, et al. An apicoplast localized ubiquitylation system is required for the import of nuclear-encoded plastid proteins. PLoS Pathog. 2013;9(6):e1003426. pmid:23785288
  30. 30. Marti M, Good RT, Rug M, Knuepfer E, Cowman AF. Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science. 2004;306(5703):1930–3. pmid:15591202
  31. 31. Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estraño C, et al. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science. 2004;306(5703):1934–7. pmid:15591203
  32. 32. Marapana DS, Dagley LF, Sandow JJ, Nebl T, Triglia T, Pasternak M, et al. Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte. Nat Microbiol. 2018;3(9):1010–22. pmid:30127496
  33. 33. Fierro MA, Muheljic A, Sha J, Wohlschlegel J, Beck JR. PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins. mSphere. 2024;9(2):e0039323. pmid:38334391
  34. 34. Polino AJ, Nasamu AS, Niles JC, Goldberg DE. Assessment of biological role and insight into druggability of the Plasmodium falciparum protease plasmepsin V. ACS Infect Dis. 2020;6(4):738–46. pmid:32069391
  35. 35. Hodder AN, Sleebs BE, Czabotar PE, Gazdik M, Xu Y, O’Neill MT, et al. Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes. Nat Struct Mol Biol. 2015;22(8):590–6. pmid:26214367
  36. 36. Cobb DW, Kudyba HM, Villegas A, Hoopmann MR, Baptista RP, Bruton B, et al. A redox-active crosslinker reveals an essential and inhibitable oxidative folding network in the endoplasmic reticulum of malaria parasites. PLoS Pathog. 2021;17(2):e1009293. pmid:33534803
  37. 37. Goerdeler F, Seeberger PH, Moscovitz O. Unveiling the sugary secrets of Plasmodium parasites. Front Microbiol. 2021;12:712538. pmid:34335547
  38. 38. Izquierdo L. The glycobiology of Plasmodium falciparum: new approaches and recent advances. Biotechnol Adv. 2023;66:108178. pmid:37216996
  39. 39. Nagar R, Garcia Castillo SS, Pinzon-Ortiz M, Patray S, Coppi A, Kanatani S, et al. The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane. J Biol Chem. 2024;300(8):107557. pmid:39002668
  40. 40. Lopaticki S, Yang ASP, John A, Scott NE, Lingford JP, O’Neill MT, et al. Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts. Nat Commun. 2017;8(1):561. pmid:28916755
  41. 41. Lopaticki S, McConville R, John A, Geoghegan N, Mohamed SD, Verzier L, et al. Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission. Nat Commun. 2022;13(1):4400. pmid:35906227
  42. 42. Nishimura T, Stefan CJ. Specialized ER membrane domains for lipid metabolism and transport. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865:158492.
  43. 43. Kilian N, Choi J-Y, Voelker DR, Ben Mamoun C. Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood. J Biol Chem. 2018;293(45):17308–16. pmid:30287688
  44. 44. Guillén-Samander A, Perepelkina N, Horáčková V, Behrens HM, Rodriguez Cruz HO, Mesén-Ramírez JP, et al. A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites. Nat Commun. 2026;17(1):3030. pmid:41904125
  45. 45. Lee J, Matuschewski K, van Dooren G, Maier AG, Rug M. Lipid droplet dynamics are essential for the development of the malaria parasite Plasmodium falciparum. J Cell Sci. 2024;137(20):jcs262162. pmid:38962997
  46. 46. Brancucci NMB, et al. Lysophosphatidylcholine regulates sexual stage differentiation in the human malaria parasite Plasmodium falciparum. Cell. 2017;171:1532-1544 e1515.
  47. 47. Singh R, Kaur N, Choubey V, Dhingra N, Kaur T. Endoplasmic reticulum stress and its role in various neurodegenerative diseases. Brain Res. 2024;1826:148742. pmid:38159591
  48. 48. Walter NS, Gorki V, Bhardwaj R, Punnakkal P. Endoplasmic reticulum Stress: implications in diseases. The Protein Journal. 2025;44:147–61.
  49. 49. Zhang M, Gallego-Delgado J, Fernandez-Arias C, Waters NC, Rodriguez A, Tsuji M, et al. Inhibiting the Plasmodium eIF2α kinase PK4 prevents artemisinin-induced latency. Cell Host Microbe. 2017;22(6):766-776.e4. pmid:29241041
  50. 50. Zhang M, Joyce BR, Sullivan WJ Jr, Nussenzweig V. Translational control in Plasmodium and toxoplasma parasites. Eukaryot Cell. 2013;12(2):161–7. pmid:23243065
  51. 51. Mok S, Ashley EA, Ferreira PE, Zhu L, Lin Z, Yeo T, et al. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science. 2015;347(6220):431–5. pmid:25502316
  52. 52. Boucher MJ, Ghosh S, Zhang L, Lal A, Jang SW, Ju A, et al. Integrative proteomics and bioinformatic prediction enable a high-confidence apicoplast proteome in malaria parasites. PLoS Biol. 2018;16(9):e2005895. pmid:30212465
  53. 53. Chisholm SA, Flores V, Kemp A, Breckels LM, Koreny L, Dos Santos Pacheco N, et al. The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles. Nat Commun. 2026;17(1):6192. pmid:42218142