Glycosome turnover in Leishmania major is mediated by autophagy

Cull, B., Prado Godinho, J. L., Fernandes Rodrigues, J. C., Frank, B., Schurigt, U., Williams, R. A.M., Coombs, G. H. and Mottram, J. C. (2014) Glycosome turnover in Leishmania major is mediated by autophagy. Autophagy, 10(12), pp. 2143-2157. (doi:10.4161/auto.36438) (PMID:25484087)

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Abstract

Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered. Quantification of RFP-SQL-labeled glycosomes showed that promastigotes of L. major possess ∼20 glycosomes per cell, whereas amastigotes contain ∼10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Δatg5 mutants, implicating autophagy in glycosome homeostasis and providing a partial explanation for the previously observed growth and virulence defects of these mutants. Use of GFP-ATG8 to label autophagosomes showed glycosomes to be cargo in ∼15% of them; glycosome-containing autophagosomes were trafficked to the lysosome for degradation. The number of autophagosomes increased 10-fold during differentiation, yet the percentage of glycosome-containing autophagosomes remained constant. This indicates that increased turnover of glycosomes was due to an overall increase in autophagy, rather than an upregulation of autophagosomes containing this cargo. Mitophagy of the single mitochondrion was not observed in L. major during normal growth or differentiation; however, mitochondrial remnants resulting from stress-induced fragmentation colocalized with autophagosomes and lysosomes, indicating that autophagy is used to recycle these damaged organelles. These data show that autophagy in Leishmania has a central role not only in maintaining cellular homeostasis and recycling damaged organelles but crucially in the adaptation to environmental change through the turnover of glycosomes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cull, Mr Benjamin and Coombs, Professor Graham and Williams, Mr Roderick and Mottram, Professor Jeremy
Authors: Cull, B., Prado Godinho, J. L., Fernandes Rodrigues, J. C., Frank, B., Schurigt, U., Williams, R. A.M., Coombs, G. H., and Mottram, J. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Autophagy
Publisher:Taylor & Francis
ISSN:1554-8627
ISSN (Online):1554-8635
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Autophagy 10(12):2143-2157
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371796The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/Z/08/ZIII - PARASITOLOGY
371798The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/B/08/ZIII - PARASITOLOGY
454141Analysing the roles of petidases in Leishmania infectivity and pathogenicityJeremy MottramMedical Research Council (MRC)G0700127III - PARASITOLOGY