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2030-01-01
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AUTOPHAGY IN PROTISTS
Ubiquitinação
Trypanosomatina
Apicomplexa
Descoberta de drogas
Diferenciação do ciclo de vida
ubiquitination
pexophagy
evolution
free-living protist
parasitic protist
life-cycle differentiation
Trypanosomatidae
Apicomplexa
drug discovery
Author
Duszenko, Michael
Ginger, Michael L.
Brennand, Ana
Gualdrón-López, Melisa
Colombo, Maria-Isabel
Coombs, Graham H.
Coppens, Isabelle
Jayabalasingham, Bamini
Langsley, Gordon
Castro, Solange Lisboa de
Menna-Barreto, Rubem
Mottram, Jeremy C.
Navarro, Miguel
Rigden, Daniel J.
Romano, Patricia S.
Stoka, Veronika
Ginger, Michael L.
Brennand, Ana
Gualdrón-López, Melisa
Colombo, Maria-Isabel
Coombs, Graham H.
Coppens, Isabelle
Jayabalasingham, Bamini
Langsley, Gordon
Castro, Solange Lisboa de
Menna-Barreto, Rubem
Mottram, Jeremy C.
Navarro, Miguel
Rigden, Daniel J.
Romano, Patricia S.
Stoka, Veronika
Affilliation
University of Tübingen. Interfaculty Institute for Biochemistry. Tübingen, Germany.
Lancaster University. School of Health and Medicine. Division of Biomedical and Life Sciences. Lancaster, UK.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. IHEM-CONICET. Mendoza, Argentina.
University of Strathclyde. Strathclyde Institute of Pharmacy and Biomedical Sciences. Glasgow, Sotland, UK.
Johns Hopkins University. Department of Molecular Microbiology and Immunology. Baltimore, MD USA.
Johns Hopkins University. Department of Molecular Microbiology and Immunology. Baltimore, MD USA.
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes; Inserm U1016-CNRS UMR8104-Université Paris-Descartes. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
University of Glasgow. College of Medical, Veterinary and Life Sciences. Wellcome Trust Centre for Molecular Parasitology Institute of Infection, Immunity and Inflammation. Glasgow, Scotland, UK.
Instituto de Parasitologia y Biomedicina “Lopez-Neyra”. CSIC. Granada, Spain.
University of Liverpool. Institute of Integrative Biology. Liverpool, UK.
Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. IHEM-CONICET. Mendoza, Argentina.
J. Stefan Institute. Department of Biochemistry and Molecular and Structural Biology. Ljubljana,Slovenia.
J. Stefan Institute. Department of Biochemistry and Molecular and Structural Biology. Ljubljana,Slovenia.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Lancaster University. School of Health and Medicine. Division of Biomedical and Life Sciences. Lancaster, UK.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. IHEM-CONICET. Mendoza, Argentina.
University of Strathclyde. Strathclyde Institute of Pharmacy and Biomedical Sciences. Glasgow, Sotland, UK.
Johns Hopkins University. Department of Molecular Microbiology and Immunology. Baltimore, MD USA.
Johns Hopkins University. Department of Molecular Microbiology and Immunology. Baltimore, MD USA.
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes; Inserm U1016-CNRS UMR8104-Université Paris-Descartes. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
University of Glasgow. College of Medical, Veterinary and Life Sciences. Wellcome Trust Centre for Molecular Parasitology Institute of Infection, Immunity and Inflammation. Glasgow, Scotland, UK.
Instituto de Parasitologia y Biomedicina “Lopez-Neyra”. CSIC. Granada, Spain.
University of Liverpool. Institute of Integrative Biology. Liverpool, UK.
Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. IHEM-CONICET. Mendoza, Argentina.
J. Stefan Institute. Department of Biochemistry and Molecular and Structural Biology. Ljubljana,Slovenia.
J. Stefan Institute. Department of Biochemistry and Molecular and Structural Biology. Ljubljana,Slovenia.
Université Catholique de Louvain. Duve Institute and Laboratory of Biochemistry. Research Unit for Tropical Diseases. Brussels, Belgium.
Abstract
Autophagy is the degradative process by which eukaryotic
cells digest their own components using acid hydrolases
within the lysosome. Originally thought to function almost
exclusively in providing starving cells with nutrients taken from
their own cellular constituents, autophagy is in fact involved in
numerous cellular events including differentiation, turnover of
macromolecules and organelles and defense against parasitic
invaders. During the past 10–20 years, molecular components
of the autophagic machinery have been discovered, revealing
a complex interactome of proteins and lipids, which, in a
concerted way, induce membrane formation to engulf cellular
material and target it for lysosomal degradation. Here, our
emphasis is autophagy in protists. We discuss experimental
and genomic data indicating that the canonical autophagy
machinery characterized in animals and fungi appeared
prior to the radiation of major eukaryotic lineages. Moreover,
we describe how comparative bioinformatics revealed that
this canonical machinery has been subject to moderation,
outright loss or elaboration on multiple occasions in protist
lineages, most probably as a consequence of diverse lifestyle
adaptations. We also review experimental studies illustrating how several pathogenic protists either utilize autophagy
mechanisms or manipulate host-cell autophagy in order to
establish or maintain infection within a host. The essentiality
of autophagy for the pathogenicity of many parasites, and the
unique features of some of the autophagy-related proteins
involved, suggest possible new targets for drug discovery.
Further studies of the molecular details of autophagy in
protists will undoubtedly enhance our understanding of the
diversity and complexity of this cellular phenomenon and the
opportunities it offers as a drug target.
Keywords in Portuguese
AutofagiaUbiquitinação
Trypanosomatina
Apicomplexa
Descoberta de drogas
Diferenciação do ciclo de vida
Keywords
autophagyubiquitination
pexophagy
evolution
free-living protist
parasitic protist
life-cycle differentiation
Trypanosomatidae
Apicomplexa
drug discovery
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