Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation

Andrew M Tomlins, Fathia Ben-Rached, Roderick Am Williams, William R Proto, Isabelle Coppens, Ulrike Ruch, Tim W Gilberger, Graham H Coombs, Jeremy C Mottram, Sylke Müller, Gordon Langsley

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Amino acid utilization is important for the growth of the erythrocytic stages of the human malaria parasite Plasmodium falciparum, however the molecular mechanism that permits survival of the parasite during conditions of limiting amino acid supply is poorly understood. We provide data here suggesting that an autophagy pathway functions in P. falciparum despite the absence of a typical lysosome for digestion of the autophagosomes. It involves PfATG8, which has a C-terminal glycine which is absolutely required for association of the protein with autophagosomes. Amino acid starvation provoked increased colocalization between PfATG8- and PfRAB7-labeled vesicles and acidification of the colabeled structures consistent with PfRAB7-mediated maturation of PfATG8-positive autophagosomes; this is a rapid process facilitating parasite survival. Immuno-electron microscopic analyses detected PfRAB7 and PfATG8 on double-membrane-bound vesicles and also near or within the parasite's food vacuole, consistent with autophagosomes fusing with the endosomal system before being routed to the food vacuole for digestion. In nonstarved parasites, PfATG8, but not PfRAB7, was found on the intact apicoplast membrane and on apicoplast-targeted vesicles and apicoplast remnants when the formation of the organelle was disrupted; a localization also requiring the C-terminal glycine. These findings suggest that in addition to a classical role in autophagy, which involves the PfRAB7-endosomal system and food vacuole, PfATG8 is associated with apicoplast-targeted vesicles and the mature apicoplast, and as such contributes to apicoplast formation and maintenance. Thus, PfATG8 may be unique in having such a second role in addition to the formation of autophagosomes required for classical autophagy.
LanguageEnglish
Pages1540 - 1552
Number of pages13
JournalAutophagy
Volume9
Issue number10
Publication statusPublished - 29 Aug 2013

Fingerprint

Apicoplasts
Autophagy
Plasmodium falciparum
Parasites
Vacuoles
Amino Acids
Food
Glycine
Digestion
Membranes
Falciparum Malaria
Starvation
Lysosomes
Organelles
Maintenance
Autophagosomes
Electrons
Growth

Keywords

  • malaria
  • food vacuole
  • endosome
  • apicoplast
  • plasmodium

Cite this

Tomlins, A. M., Ben-Rached, F., Williams, R. A., Proto, W. R., Coppens, I., Ruch, U., ... Langsley, G. (2013). Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation. Autophagy, 9(10), 1540 - 1552.
Tomlins, Andrew M ; Ben-Rached, Fathia ; Williams, Roderick Am ; Proto, William R ; Coppens, Isabelle ; Ruch, Ulrike ; Gilberger, Tim W ; Coombs, Graham H ; Mottram, Jeremy C ; Müller, Sylke ; Langsley, Gordon. / Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation. In: Autophagy. 2013 ; Vol. 9, No. 10. pp. 1540 - 1552.
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Tomlins, AM, Ben-Rached, F, Williams, RA, Proto, WR, Coppens, I, Ruch, U, Gilberger, TW, Coombs, GH, Mottram, JC, Müller, S & Langsley, G 2013, 'Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation' Autophagy, vol. 9, no. 10, pp. 1540 - 1552.

Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation. / Tomlins, Andrew M; Ben-Rached, Fathia; Williams, Roderick Am; Proto, William R; Coppens, Isabelle; Ruch, Ulrike; Gilberger, Tim W; Coombs, Graham H; Mottram, Jeremy C; Müller, Sylke; Langsley, Gordon.

In: Autophagy, Vol. 9, No. 10, 29.08.2013, p. 1540 - 1552.

Research output: Contribution to journalArticle

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T1 - Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation

AU - Tomlins, Andrew M

AU - Ben-Rached, Fathia

AU - Williams, Roderick Am

AU - Proto, William R

AU - Coppens, Isabelle

AU - Ruch, Ulrike

AU - Gilberger, Tim W

AU - Coombs, Graham H

AU - Mottram, Jeremy C

AU - Müller, Sylke

AU - Langsley, Gordon

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N2 - Amino acid utilization is important for the growth of the erythrocytic stages of the human malaria parasite Plasmodium falciparum, however the molecular mechanism that permits survival of the parasite during conditions of limiting amino acid supply is poorly understood. We provide data here suggesting that an autophagy pathway functions in P. falciparum despite the absence of a typical lysosome for digestion of the autophagosomes. It involves PfATG8, which has a C-terminal glycine which is absolutely required for association of the protein with autophagosomes. Amino acid starvation provoked increased colocalization between PfATG8- and PfRAB7-labeled vesicles and acidification of the colabeled structures consistent with PfRAB7-mediated maturation of PfATG8-positive autophagosomes; this is a rapid process facilitating parasite survival. Immuno-electron microscopic analyses detected PfRAB7 and PfATG8 on double-membrane-bound vesicles and also near or within the parasite's food vacuole, consistent with autophagosomes fusing with the endosomal system before being routed to the food vacuole for digestion. In nonstarved parasites, PfATG8, but not PfRAB7, was found on the intact apicoplast membrane and on apicoplast-targeted vesicles and apicoplast remnants when the formation of the organelle was disrupted; a localization also requiring the C-terminal glycine. These findings suggest that in addition to a classical role in autophagy, which involves the PfRAB7-endosomal system and food vacuole, PfATG8 is associated with apicoplast-targeted vesicles and the mature apicoplast, and as such contributes to apicoplast formation and maintenance. Thus, PfATG8 may be unique in having such a second role in addition to the formation of autophagosomes required for classical autophagy.

AB - Amino acid utilization is important for the growth of the erythrocytic stages of the human malaria parasite Plasmodium falciparum, however the molecular mechanism that permits survival of the parasite during conditions of limiting amino acid supply is poorly understood. We provide data here suggesting that an autophagy pathway functions in P. falciparum despite the absence of a typical lysosome for digestion of the autophagosomes. It involves PfATG8, which has a C-terminal glycine which is absolutely required for association of the protein with autophagosomes. Amino acid starvation provoked increased colocalization between PfATG8- and PfRAB7-labeled vesicles and acidification of the colabeled structures consistent with PfRAB7-mediated maturation of PfATG8-positive autophagosomes; this is a rapid process facilitating parasite survival. Immuno-electron microscopic analyses detected PfRAB7 and PfATG8 on double-membrane-bound vesicles and also near or within the parasite's food vacuole, consistent with autophagosomes fusing with the endosomal system before being routed to the food vacuole for digestion. In nonstarved parasites, PfATG8, but not PfRAB7, was found on the intact apicoplast membrane and on apicoplast-targeted vesicles and apicoplast remnants when the formation of the organelle was disrupted; a localization also requiring the C-terminal glycine. These findings suggest that in addition to a classical role in autophagy, which involves the PfRAB7-endosomal system and food vacuole, PfATG8 is associated with apicoplast-targeted vesicles and the mature apicoplast, and as such contributes to apicoplast formation and maintenance. Thus, PfATG8 may be unique in having such a second role in addition to the formation of autophagosomes required for classical autophagy.

KW - malaria

KW - food vacuole

KW - endosome

KW - apicoplast

KW - plasmodium

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Tomlins AM, Ben-Rached F, Williams RA, Proto WR, Coppens I, Ruch U et al. Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation. Autophagy. 2013 Aug 29;9(10):1540 - 1552.