Autophagy is involved in nutritional stress response and differentiation in Trypanosoma cruzi.
Autophagy is the major mechanism used by eukaryotic cells to degrade and recycle proteins and organelles. Bioinformatics analysis of the genome of the protozoan parasite Trypanosoma cruzi revealed the presence of all components of the Atg8 conjugation system, whereas Atg12, Atg5, and Atg10 as the major components of the Atg12 pathway could not be identified. The two TcATG4 (autophagin) homologs present in the genome were found to correctly process the two ATG8 homologs after the conserved Gly residue. Functional studies revealed that both ATG4 homologues but only one T. cruzi ATG8 homolog (TcATG8.1) complemented yeast deletion strains. During starvation of the parasite, TcAtg8.1, but not TcAtg8.2, was found by immunofluorescence to be located in autophagosome-like vesicles. This confirms its function as an Atg8/LC3 homolog and its potential to be used as an autophagosomal marker. Most importantly, autophagy is involved in differentiation between developmental stages of T. cruzi, a process that is essential for parasite maintenance and survival. These findings suggest that the autophagy pathway could represent a target for a novel chemotherapeutic strategy against Chagas disease.
Instituto de Investigaciones Biotecnologicas (IIB/INTECH, Universidad Nacional de San Martín/Consejo Nacional de Investigaciones Científicas y Técnicas), 1650 San Martin, Buenos Aires, Argentina.
Vanina E
VE
Alvarez
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, SI 1000, Ljubljana, Slovenia.
Gregor
G
Kosec
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, Ilha do Fundão, 21949-900 Rio de Janeiro-RJ, Brazil.
Celso
C
Sant'Anna
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, SI 1000, Ljubljana, Slovenia.
Vito
V
Turk
Instituto de Investigaciones Biotecnologicas (IIB/INTECH, Universidad Nacional de San Martín/Consejo Nacional de Investigaciones Científicas y Técnicas), 1650 San Martin, Buenos Aires, Argentina.
Juan J
JJ
Cazzulo
Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, SI 1000, Ljubljana, Slovenia. Electronic address: boris.turk@ijs.si.
Boris
B
Turk
D000818:Animals; D001343:Autophagy; D002474:Cell-Free System; D019295:Computational Biology / Q000379:methods; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D018503:Genome, Protozoan; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000737:chemistry* / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry; D014162:Transfection; D014349:Trypanosoma cruzi / Q000378:metabolism / Q000502:physiology*
D015800:Protozoan Proteins; D011994:Recombinant Proteins