Glycosome turnover in Leishmania major is mediated by autophagy

Benjamin Cull, Joseane Lima Prado Godinho, Juliany Cola Fernandes Rodrigues, Benjamin Frank, Uta Schurigt, Roderick A. M. Williams, Graham H. Coombs, Jeremy C. Mottram

Research output: Contribution to journalArticle

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 similar to 20 glycosomes per cell, whereas amastigotes contain similar to 10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Delta atg5 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 similar to 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.
Original languageEnglish
Pages (from-to)2143-2157
JournalAutophagy
Volume10
Issue number12
DOIs
Publication statusPublished - Dec 2014

Keywords

  • adaptation
  • ATG8
  • autophagy
  • glycosome
  • Leishmania
  • protozoan parasite

Cite this

Cull, B., Prado Godinho, J. L., Fernandes Rodrigues, J. C., Frank, B., Schurigt, U., Williams, R. A. M., ... Mottram, J. C. (2014). Glycosome turnover in Leishmania major is mediated by autophagy. Autophagy, 10(12), 2143-2157. https://doi.org/10.4161/auto.36438
Cull, Benjamin ; Prado Godinho, Joseane Lima ; Fernandes Rodrigues, Juliany Cola ; Frank, Benjamin ; Schurigt, Uta ; Williams, Roderick A. M. ; Coombs, Graham H. ; Mottram, Jeremy C. / Glycosome turnover in Leishmania major is mediated by autophagy. In: Autophagy. 2014 ; Vol. 10, No. 12. pp. 2143-2157.
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Cull, B, Prado Godinho, JL, Fernandes Rodrigues, JC, Frank, B, Schurigt, U, Williams, RAM, Coombs, GH & Mottram, JC 2014, 'Glycosome turnover in Leishmania major is mediated by autophagy' Autophagy, vol. 10, no. 12, pp. 2143-2157. https://doi.org/10.4161/auto.36438

Glycosome turnover in Leishmania major is mediated by autophagy. / Cull, Benjamin; Prado Godinho, Joseane Lima; Fernandes Rodrigues, Juliany Cola; Frank, Benjamin; Schurigt, Uta; Williams, Roderick A. M.; Coombs, Graham H.; Mottram, Jeremy C.

In: Autophagy, Vol. 10, No. 12, 12.2014, p. 2143-2157.

Research output: Contribution to journalArticle

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AU - Cull, Benjamin

AU - Prado Godinho, Joseane Lima

AU - Fernandes Rodrigues, Juliany Cola

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AU - Williams, Roderick A. M.

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AU - Mottram, Jeremy C.

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AB - 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 similar to 20 glycosomes per cell, whereas amastigotes contain similar to 10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Delta atg5 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 similar to 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.

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KW - ATG8

KW - autophagy

KW - glycosome

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KW - protozoan parasite

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DO - 10.4161/auto.36438

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JO - Autophagy

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Cull B, Prado Godinho JL, Fernandes Rodrigues JC, Frank B, Schurigt U, Williams RAM et al. Glycosome turnover in Leishmania major is mediated by autophagy. Autophagy. 2014 Dec;10(12):2143-2157. https://doi.org/10.4161/auto.36438