Autophagy in parasitic protists: Unique features and drug targets

Ana Brennand, Melisa Gualdrón-López, Isabelle Coppens, Daniel J. Rigden, Michael L. Ginger, Paul A M Michels

Research output: Contribution to journalReview article

77 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages83-99
Number of pages17
JournalMolecular and Biochemical Parasitology
Volume177
Issue number2
Early online date10 Feb 2011
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

Fingerprint

Autophagy
Pharmaceutical Preparations
Parasites
Life Cycle Stages
Organelles
Virulence
Proteins
Sporozoites
Giardia lamblia
Trophozoites
Drug Design
Eukaryotic Cells
Hydrolases
Drug Delivery Systems
Starvation
Lysosomes
Cues
Saccharomyces cerevisiae
Cell Differentiation
Hepatocytes

Cite this

Brennand, A., Gualdrón-López, M., Coppens, I., Rigden, D. J., Ginger, M. L., & Michels, P. A. M. (2011). Autophagy in parasitic protists: Unique features and drug targets. Molecular and Biochemical Parasitology, 177(2), 83-99. https://doi.org/10.1016/j.molbiopara.2011.02.003
Brennand, Ana ; Gualdrón-López, Melisa ; Coppens, Isabelle ; Rigden, Daniel J. ; Ginger, Michael L. ; Michels, Paul A M. / Autophagy in parasitic protists : Unique features and drug targets. In: Molecular and Biochemical Parasitology. 2011 ; Vol. 177, No. 2. pp. 83-99.
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Brennand, A, Gualdrón-López, M, Coppens, I, Rigden, DJ, Ginger, ML & Michels, PAM 2011, 'Autophagy in parasitic protists: Unique features and drug targets', Molecular and Biochemical Parasitology, vol. 177, no. 2, pp. 83-99. https://doi.org/10.1016/j.molbiopara.2011.02.003

Autophagy in parasitic protists : Unique features and drug targets. / Brennand, Ana; Gualdrón-López, Melisa; Coppens, Isabelle; Rigden, Daniel J.; Ginger, Michael L.; Michels, Paul A M.

In: Molecular and Biochemical Parasitology, Vol. 177, No. 2, 01.06.2011, p. 83-99.

Research output: Contribution to journalReview article

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AU - Ginger, Michael L.

AU - Michels, Paul A M

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