Autophagy in parasitic protists: unique features and drug targets.


:Eukaryotic cells can degrade their own components, cytosolic proteins and organelles, using dedicated hydrolases contained within the acidic interior of their lysosomes. This degradative process, called autophagy, is used under starvation conditions to recycle redundant or less important macromolecules, facilitates metabolic re-modeling in response to environmental cues, and is also often important during cell differentiation. In this review, we discuss the role played by autophagy during the life cycles of the major parasitic protists. To provide context, we also provide an overview of the different forms of autophagy and the successive steps in the autophagic processes, including the proteins involved, as revealed in recent decades by studies using the model organism Saccharomyces cerevisiae, methylotrophic yeasts and mammalian cells. We describe for trypanosomatid parasites how autophagy plays a role in the differentiation from one life cycle stage to the next one and, in the case of the intracellular parasites, for virulence. For malarial parasites, although only a limited repertoire of canonical autophagy-related proteins can be detected, autophagy seems to play a role in the removal of redundant organelles important for cell invasion, when sporozoites develop into intracellular trophozoites inside the hepatocytes. The complete absence of a canonical autophagy pathway from the microaerophile Giardia lamblia is also discussed. Finally, the essential role of autophagy for differentiation and pathogenicity of some pathogenic protists suggests that the proteins involved in this process may represent new targets for drug development. Opportunities and strategies for drug design targeting autophagy proteins are discussed.


Mol Biochem Parasitol


Brennand A,Gualdrón-López M,Coppens I,Rigden DJ,Ginger ML,Michels PA




Has Abstract


2011-06-01 00:00:00














  • Assessment of pfmdr 1 gene copy number by tandem competitive polymerase chain reaction.

    abstract::The pfmdr 1 gene encodes a Plasmodium falciparum homologue of the human P-glycoprotein expressed on the surface of the parasite food vacuole. Variation in copy number and specific codon mutations of pfmdr 1 have been implicated in the development of parasite resistance to antimalarial drugs. We describe here the techn...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Price R,Robinson G,Brockman A,Cowman A,Krishna S

    更新日期:1997-04-01 00:00:00

  • Differential toxicity of ricin and diphtheria toxin for bloodstream forms of Trypanosoma brucei.

    abstract::The cytotoxicity of ricin and diphtheria toxin was studied in culture-adapted bloodstream forms of Trypanosoma brucei. Although ricin is endocytosed at a rate comparable to that of other internalized macromolecules, it is nontoxic to bloodstream-form trypanosomes. The resistance lies partly in low susceptibility of th...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Scory S,Steverding D

    更新日期:1997-12-01 00:00:00

  • Molecular species analysis and quantification of the glycosylphosphatidylinositol intermediate glycolipid C from Trypanosoma brucei.

    abstract::The precursor of the glycosylphosphatidylinositol membrane anchor of the variant surface glycoprotein of Trypanosoma brucei is known as glycolipid A and it has the structure: EtN-PO4-6Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol-PO4-(sn-1,2-dimyristoylglycerol). This precursor exists in equilibriu...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Güther ML,Treumann A,Ferguson MA

    更新日期:1996-05-01 00:00:00

  • DNA microarrays for comparative genomics and analysis of gene expression in Trypanosoma cruzi.

    abstract::Trypanosoma cruzi presents high genetic diversity and parasite isolates show remarkable differences in biological parameters. In this study, we evaluated whether DNA microarrays containing CL Brener cDNAs can be used for comparative genomics and for the analysis of gene expression in T. cruzi. We constructed a prototy...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Baptista CS,Vêncio RZ,Abdala S,Valadares MP,Martins C,de Bragança Pereira CA,Zingales B

    更新日期:2004-12-01 00:00:00

  • Trypanosoma cruzi poly-zinc finger protein: a novel DNA/RNA-binding CCHC-zinc finger protein.

    abstract::A poly-zinc finger protein, designated PZFP1 was identified in Trypanosoma cruzi for the first time. The protein has 191 amino acids, contains seven motifs Cys(X)(2)Cys(X)(4)His(X)(4)Cys. A recombinant PZFP1 was generated in E. coli and the expected 21kDa polypeptide co-purified with two other inducible products of ab...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Espinosa JM,Portal D,Lobo GS,Pereira CA,Alonso GD,Gómez EB,Lan GH,Pomar RV,Flawiá MM,Torres HN

    更新日期:2003-09-01 00:00:00

  • The free amino acid pool in Leishmania tropica promastigotes.

    abstract::The principal constituents of the free amino acid pool in Leishmania tropica promastigotes include alanine, glycine, serine, threonine, alpha-aminobutyric acid and ethanolamine. Changes in levels of the pool constituents during starvation, nutrient supplementation and treatment with a metabolic inhibitor (sodium fluor...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Simon MW,Jayasimhulu K,Mukkada AJ

    更新日期:1983-09-01 00:00:00

  • Differences in the surface radioiodinated proteins of skin and uterine microfilariae of Onchocerca gibsoni.

    abstract::Surface labeling studies using two populations of Onchocerca gibsoni microfilariae revealed important differences in major radioiodinated proteins. Small numbers of microfilariae harvested from the skin of cattle or the uteri of adult worms from skin nodules were purified, radioiodinated, solubilized and the proteins ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Forsyth KP,Copeman DB,Mitchell GF

    更新日期:1984-02-01 00:00:00

  • Molecular cloning and characterization of the polypeptide backbone of Schistosoma mansoni circulating cathodic antigen.

    abstract::One of the candidate schistosome antigens for the development of a circulating antigen detection diagnostic assay is the circulating cathodic antigen (CCA). Detection of CCA in urine provides a non-invasive assay with high sensitivity. Previously we reported that CCA is secreted in patients' urine as a small molecular...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Abdeen HH,Attallah AF,Mansour MM,Harrison RA

    更新日期:1999-06-25 00:00:00

  • A Plasmodium multi-domain protein possesses multiple inositol phosphate kinase activities.

    abstract::The synchronization of intraerythrocytic maturation of Plasmodium parasites is an important factor in the malaria infection process. Synchronization is mediated by inositol phosphate (InsP(x))-induced Ca(2+)-release from internal stores. To further investigate the InsP(x) metabolism in these parasites a Plasmodium pro...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Stritzke C,Nalaskowski MM,Fanick W,Lin H,Mayr GW

    更新日期:2012-12-01 00:00:00

  • Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen.

    abstract::Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable d...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Hall R,Hunt PD,Carrington M,Simmons D,Williamson S,Mecham RP,Tait A

    更新日期:1992-07-01 00:00:00

  • Interleukin-8-like activity in a filarial asparaginyl-tRNA synthetase.

    abstract::A wide range of secondary biological functions have been documented for eukaryotic aminoacyl-tRNA synthetases including roles in transcriptional regulation, mitochondrial RNA splicing, cell growth, and chemokine-like activities. The asparaginyl-tRNA synthetase (AsnRS) of the filarial nematode, Brugia malayi, is a high...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Kron MA,Wang C,Vodanovic-Jankovic S,Howard OM,Kuhn LA

    更新日期:2012-09-01 00:00:00

  • Characterization of a Giardia lamblia variant-specific surface protein (VSP) gene from isolate GS/M and estimation of the VSP gene repertoire size.

    abstract::Giardia lamblia undergoes surface antigenic variation. The variant-specific surface proteins (VSPs) of isolate WB are cysteine-rich, can vary dramatically in size, contain Cys-X-X-Cys motifs, and are differentially expressed. GS/M(H7) is a Giardia clone from a different isolate which expresses a VSP epitope not found ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Nash TE,Mowatt MR

    更新日期:1992-04-01 00:00:00

  • Identification of peripheral membrane proteins associated with the tubo-vesicular network of Plasmodium falciparum infected erythrocytes.

    abstract::During intracellular development of the malarial parasite numerous membranous vesicles appear in the infected erythrocyte cytoplasm between the parasitophorous vacuolar membrane (PVM) and the erythrocyte plasma membrane. In this study we describe the characterization of a monoclonal antibody which recognizes two major...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Martinez SL,Clavijo CA,Winograd E

    更新日期:1998-03-15 00:00:00

  • Identification of novel splice variants of the voltage- and Ca²⁺-dependent K⁺-channel SLO-1 of Trichuris muris.

    abstract::The anthelmintic cyclooctadepsipeptide emodepside is effective against nematodes showing resistance against established drug classes. Emodepside exerts its nematicidal effects mainly through its validated target, the tetrameric voltage- and calcium-activated potassium channel SLO-1. Two slo-1 genes were described in T...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Yilmaz E,Kulke D,von Samson-Himmelstjerna G,Krücken J

    更新日期:2015-01-01 00:00:00

  • Characterisation of the gene encoding a 104-kilodalton microneme-rhoptry protein of Theileria parva.

    abstract::A neutralizing antiserum, C16, raised against sporozoites of Theileria parva parva was used to screen a lambda gt11 expression library of T. parva parva (Muguga) genomic DNA fragments. Proteins encoded by one phage clone, lambda TpS-17, were reactive with the C16 antiserum. Detailed characterisation of the DNA insert ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Iams KP,Young JR,Nene V,Desai J,Webster P,ole-MoiYoi OK,Musoke AJ

    更新日期:1990-02-01 00:00:00

  • Molecular and functional characterisation of the heat shock protein 10 of Strongyloides ratti.

    abstract::Strongyloides stercoralis and S. ratti are intestinal parasitic nematodes infecting rats and humans, respectively. Both present extraordinary life cycles comprising a free-living generation in addition to parasitic stages. In search of molecules possibly involved in parasite-host interaction, we performed mass spectro...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Tazir Y,Steisslinger V,Soblik H,Younis AE,Beckmann S,Grevelding CG,Steen H,Brattig NW,Erttmann KD

    更新日期:2009-12-01 00:00:00

  • Protein variation in clones of Plasmodium falciparum detected by two dimensional electrophoresis.

    abstract::Two dimensional electrophoresis has been used to examine protein variation in clones of two Plasmodium falciparum isolates. Variant forms of 12 proteins were detected. Five genetically distinct parasite types were identified in one isolate, and two in the second isolate. Examination of uncloned parasites using this te...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Fenton B,Walker A,Walliker D

    更新日期:1985-08-01 00:00:00

  • Cathepsin B-like cysteine proteases of Leishmania mexicana.

    abstract::A group of Leishmania mexicana cysteine proteases that differ from those previously found in this protozoon are described. The enzymes characteristically have a preference for peptidyl substrates with a phenylalanyl-valyl-arginyl moiety, do not hydrolyse gelatin in substrate-sodium dodecyl sulphate polyacrylamide gels...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Robertson CD,Coombs GH

    更新日期:1993-12-01 00:00:00

  • Identification and localization of a Novel Invasin of Plasmodium falciparum.

    abstract::Plasmodium falciparum is the causative organism for the most severe form of malaria among humans. The clinical symptoms are accredited to the asexual stage of parasite life cycle, involving merozoite invasion of erythrocyte, development and re-invasion into the new erythrocyte. Interaction of parasite proteins present...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Hans N,Relan U,Dubey N,Gaur D,Chauhan VS

    更新日期:2015-08-01 00:00:00

  • The biochemical and immunochemical characterisation of the 30 kilodalton surface antigen of Brugia pahangi.

    abstract::The major surface antigen (30 kDa) of Brugia pahangi has been characterised by a number of biochemical and immunochemical means. The 30 kDa polypeptide is a glycoprotein which can be extracted from the worm surface by homogenization in the absence of detergents. The 30 kDa polypeptide can be metabolically labelled wit...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Devaney E

    更新日期:1988-01-01 00:00:00

  • The secreted and somatic antigens of the third stage larva of Anisakis simplex, and antigenic relationship with Ascaris suum, Ascaris lumbricoides, and Toxocara canis.

    abstract::The in vitro-released 'excretory/secretory' (ES) and somatic antigens of the third stage (infective) larva of Anisakis simplex were characterised by radioiodination, immunoprecipitation, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Oral infection with the parasite elicited a substantial IgG antibody...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Kennedy MW,Tierney J,Ye P,McMonagle FA,McIntosh A,McLaughlin D,Smith JW

    更新日期:1988-10-01 00:00:00

  • Arp1, an actin-related protein, in Plasmodium berghei.

    abstract::Actin-related proteins (Arps) constitute a family of eukaryotic cytoskeletal proteins involved in such diverse events as cell motility, cytokinesis, vesicle transport, and chromatin remodelling. Previously, in a study of Plasmodium berghei gene expression in ookinetes and oocysts, we detected stage-specific increased ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Siden-Kiamos I,Schüler H,Liakopoulos D,Louis C

    更新日期:2010-10-01 00:00:00

  • Characterization of phosphodiesterase-5 as a surface protein in the tegument of Schistosoma mansoni.

    abstract::Schistosoma mansoni is a major causative agent of schistosomiasis, an important parasitic disease that constitutes a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection and the development of an effective vaccine still remains the most desirable me...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Rofatto HK,Tararam CA,Borges WC,Wilson RA,Leite LC,Farias LP

    更新日期:2009-07-01 00:00:00

  • Characterization of a SR protein from Trypanosoma brucei with homology to RNA-binding cis-splicing proteins.

    abstract::The protozoan parasite Trypanosoma brucei relies on trans-splicing to process its mRNAs. A novel nuclear serine/arginine (SR)-rich trypanosomal protein (TSR1) was characterized which contains two RNA recognition motifs. The TSR1 protein appears to be homologous to RNA-binding SR proteins of the cis-splicing machinery ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Ismaïli N,Pérez-Morga D,Walsh P,Mayeda A,Pays A,Tebabi P,Krainer AR,Pays E

    更新日期:1999-07-30 00:00:00

  • Quantitation of genetic differences between Trypanosoma brucei gambiense, rhodesiense and brucei by restriction enzyme analysis of kinetoplast DNA.

    abstract::We have compared a total of 44 recognition sites for 12 restriction endonucleases on the 20 kilobase pair maxi-circle of kinetoplast DNA from nine Trypanosoma brucei stocks, four which are known to be infective to man (tow 'gambiense' and two 'rhodesiense' variants). In addition to five polymorphic sites, these DNAs d...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Borst P,Fase-Fowler F,Gibson WC

    更新日期:1981-06-01 00:00:00

  • The FAR proteins of filarial nematodes: secretion, glycosylation and lipid binding characteristics.

    abstract::The FAR proteins of nematodes are small ( approximately 20 kDa), helix-rich, fatty acid and retinol-binding (FAR) proteins that appear to be confined to nematodes. We have carried out a comparative sequence and biochemical analysis of selected FAR proteins often species of filarial parasites (from the genera Onchocerc...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Garofalo A,Kläger SL,Rowlinson MC,Nirmalan N,Klion A,Allen JE,Kennedy MW,Bradley JE

    更新日期:2002-07-01 00:00:00

  • Unusual diversity in alpha-amanitin sensitivity of RNA polymerases in trichomonads.

    abstract::Previous studies in the parasitic protist Trichomonas vaginalis have revealed that protein coding genes are transcribed by an alpha-amanitin-resistant RNA polymerase (RNAP) II. To investigate whether this unusual property is a general characteristic of trichomonads, we addressed the physiology of RNA synthesis in lyso...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Vanácová S,Tachezy J,Ullu E,Tschudi C

    更新日期:2001-07-01 00:00:00

  • Preference of A/T ending codons in mitochondrial ATP6 gene under phylum Platyhelminthes: Codon usage of ATP6 gene in Platyhelminthes.

    abstract::Unequal usage of synonymous codons in the gene transcript for an amino acid is known as codon usage bias (CUB). It is a unique property of gene as well as genome. Mutation and natural selection are known to be the major factors that influence CUB. Other factors encompass gene expression level, GC content, codon positi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Mazumder GA,Uddin A,Chakraborty S

    更新日期:2018-10-01 00:00:00

  • Energy metabolism in Cotugnia digonopora and the effect of anthelmintics.

    abstract::Incorporation of 32Pi into organic phosphate by mitochondria of Cotugnia digonopora was supported maximally by malate. Fumarate and succinate induced lower but significant production of ATP. Pyruvate, alpha-ketoglutarate and oxalacetate proved to be poor substrates and citrate and isocitrate had no effect. A net phosp...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Pampori NA,Singh G,Srivastava VM

    更新日期:1984-04-01 00:00:00

  • Characterization of a polymorphic family of integral membrane proteins in promastigotes of different Leishmania species.

    abstract::Antibodies raised against a Leishmania major recombinant promastigote surface antigen 2 (PSA-2) fragment recognized three major polypeptides of approximate M(r) 96,000, 80,000 and 50,000 in promastigotes of three Israeli isolates of L. major including the cloned line LRC-L137-V121, but detected a different array of po...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章


    authors: Symons FM,Murray PJ,Ji H,Simpson RJ,Osborn AH,Cappai R,Handman E

    更新日期:1994-09-01 00:00:00