TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.

Autores
Loos, Julia Alexandra; Negro, Perla Susana; Cumino, Andrea Carina
Año de publicación
2022
Idioma
español castellano
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Evolutionary conserved insulin/TOR pathway is an essential network of outputs and effectors for the development of Echinococcus larval stage. Molecular and biochemical assays, allowed us to corroborate the parasite-derived insulin receptors and host´s insulin interaction. The insulin signaling regulates anabolic functions in metacestodes and protoscoleces, suggesting the insulin/TORC1 activation. Insulin treatment activates downstream signaling components, such as phosphorylation of parasite AKT and TOR, which leads to nutrients uptake, overexpression of glucose transporters, induction of mitochondrial metabolism, and lipid droplet and glycogen synthesis stimulation, both crucial reserve molecules in this cestode. Similar to its orthologs, Echinococcus-TOR is a high-molecular-weight protein that contains all preserved structural domains, with two conserved insulin-dependent phosphorylation hot spots (Thr3119- Ser3122) likewise to vertebrate. However, Echinococcus-TOR, possess an additional peptide with coil structure into regulatory domain, similarly others parasite helminths, with potential druggability and specificity for TOR kinase. Furthermore, we analyzed in which manner the inactivation of TORC1 induces autophagy and arrests the parasites survival. Indirect inhibition of TORC1 in presence of metformin, causes an increase in autophagy genes transcription, through overexpression and activation of transcription factor EB (TFEB), whose phospho-activation and nuclear translocation is TORC1-dependent. TFEB is a master regulator that controls essential processes in the life cycle of Echinococcus sp. as the endo-exocytosis (necessary in absence of digestive/excretory systems) and the biogenesis of autophagy key organelles as autophagosomes and lysosomes (given conditions of constant nutrient deficiency). Lastly, based on electron microscopy data, we showed that TFEB may induce ER-phagy in metformin-treated parasites, previous identification of ER specific receptors.
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Negro, Perla Susana. Universidad Nacional de Rosario. Facultad de Ciencias Veterinarias; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
IX Congreso Argentino de Parasitología
Salta
Argentina
Asociación Parasitológica Argentina
Materia
Echinococcus sp.
TOR
insulin
glucagon
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/250398
Acceder
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network_name_str CONICET Digital (CONICET)
spelling TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.Loos, Julia AlexandraNegro, Perla SusanaCumino, Andrea CarinaEchinococcus sp.TORinsulinglucagonhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Evolutionary conserved insulin/TOR pathway is an essential network of outputs and effectors for the development of Echinococcus larval stage. Molecular and biochemical assays, allowed us to corroborate the parasite-derived insulin receptors and host´s insulin interaction. The insulin signaling regulates anabolic functions in metacestodes and protoscoleces, suggesting the insulin/TORC1 activation. Insulin treatment activates downstream signaling components, such as phosphorylation of parasite AKT and TOR, which leads to nutrients uptake, overexpression of glucose transporters, induction of mitochondrial metabolism, and lipid droplet and glycogen synthesis stimulation, both crucial reserve molecules in this cestode. Similar to its orthologs, Echinococcus-TOR is a high-molecular-weight protein that contains all preserved structural domains, with two conserved insulin-dependent phosphorylation hot spots (Thr3119- Ser3122) likewise to vertebrate. However, Echinococcus-TOR, possess an additional peptide with coil structure into regulatory domain, similarly others parasite helminths, with potential druggability and specificity for TOR kinase. Furthermore, we analyzed in which manner the inactivation of TORC1 induces autophagy and arrests the parasites survival. Indirect inhibition of TORC1 in presence of metformin, causes an increase in autophagy genes transcription, through overexpression and activation of transcription factor EB (TFEB), whose phospho-activation and nuclear translocation is TORC1-dependent. TFEB is a master regulator that controls essential processes in the life cycle of Echinococcus sp. as the endo-exocytosis (necessary in absence of digestive/excretory systems) and the biogenesis of autophagy key organelles as autophagosomes and lysosomes (given conditions of constant nutrient deficiency). Lastly, based on electron microscopy data, we showed that TFEB may induce ER-phagy in metformin-treated parasites, previous identification of ER specific receptors.Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaFil: Negro, Perla Susana. Universidad Nacional de Rosario. Facultad de Ciencias Veterinarias; ArgentinaFil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; ArgentinaIX Congreso Argentino de ParasitologíaSaltaArgentinaAsociación Parasitológica ArgentinaAsociación Parasitológica Argentina2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/250398TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.; IX Congreso Argentino de Parasitología; Salta; Argentina; 2022; 94-94CONICET DigitalCONICETspaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:42:36Zoai:ri.conicet.gov.ar:11336/250398instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:42:37.136CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
title TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
spellingShingle TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
Loos, Julia Alexandra
Echinococcus sp.
TOR
insulin
glucagon
title_short TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
title_full TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
title_fullStr TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
title_full_unstemmed TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
title_sort TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.
dc.creator.none.fl_str_mv Loos, Julia Alexandra
Negro, Perla Susana
Cumino, Andrea Carina
author Loos, Julia Alexandra
author_facet Loos, Julia Alexandra
Negro, Perla Susana
Cumino, Andrea Carina
author_role author
author2 Negro, Perla Susana
Cumino, Andrea Carina
author2_role author
author
dc.subject.none.fl_str_mv Echinococcus sp.
TOR
insulin
glucagon
topic Echinococcus sp.
TOR
insulin
glucagon
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Evolutionary conserved insulin/TOR pathway is an essential network of outputs and effectors for the development of Echinococcus larval stage. Molecular and biochemical assays, allowed us to corroborate the parasite-derived insulin receptors and host´s insulin interaction. The insulin signaling regulates anabolic functions in metacestodes and protoscoleces, suggesting the insulin/TORC1 activation. Insulin treatment activates downstream signaling components, such as phosphorylation of parasite AKT and TOR, which leads to nutrients uptake, overexpression of glucose transporters, induction of mitochondrial metabolism, and lipid droplet and glycogen synthesis stimulation, both crucial reserve molecules in this cestode. Similar to its orthologs, Echinococcus-TOR is a high-molecular-weight protein that contains all preserved structural domains, with two conserved insulin-dependent phosphorylation hot spots (Thr3119- Ser3122) likewise to vertebrate. However, Echinococcus-TOR, possess an additional peptide with coil structure into regulatory domain, similarly others parasite helminths, with potential druggability and specificity for TOR kinase. Furthermore, we analyzed in which manner the inactivation of TORC1 induces autophagy and arrests the parasites survival. Indirect inhibition of TORC1 in presence of metformin, causes an increase in autophagy genes transcription, through overexpression and activation of transcription factor EB (TFEB), whose phospho-activation and nuclear translocation is TORC1-dependent. TFEB is a master regulator that controls essential processes in the life cycle of Echinococcus sp. as the endo-exocytosis (necessary in absence of digestive/excretory systems) and the biogenesis of autophagy key organelles as autophagosomes and lysosomes (given conditions of constant nutrient deficiency). Lastly, based on electron microscopy data, we showed that TFEB may induce ER-phagy in metformin-treated parasites, previous identification of ER specific receptors.
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
Fil: Negro, Perla Susana. Universidad Nacional de Rosario. Facultad de Ciencias Veterinarias; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mar del Plata. Instituto de Investigaciones En Produccion, Sanidad y Ambiente.; Argentina
IX Congreso Argentino de Parasitología
Salta
Argentina
Asociación Parasitológica Argentina
description Evolutionary conserved insulin/TOR pathway is an essential network of outputs and effectors for the development of Echinococcus larval stage. Molecular and biochemical assays, allowed us to corroborate the parasite-derived insulin receptors and host´s insulin interaction. The insulin signaling regulates anabolic functions in metacestodes and protoscoleces, suggesting the insulin/TORC1 activation. Insulin treatment activates downstream signaling components, such as phosphorylation of parasite AKT and TOR, which leads to nutrients uptake, overexpression of glucose transporters, induction of mitochondrial metabolism, and lipid droplet and glycogen synthesis stimulation, both crucial reserve molecules in this cestode. Similar to its orthologs, Echinococcus-TOR is a high-molecular-weight protein that contains all preserved structural domains, with two conserved insulin-dependent phosphorylation hot spots (Thr3119- Ser3122) likewise to vertebrate. However, Echinococcus-TOR, possess an additional peptide with coil structure into regulatory domain, similarly others parasite helminths, with potential druggability and specificity for TOR kinase. Furthermore, we analyzed in which manner the inactivation of TORC1 induces autophagy and arrests the parasites survival. Indirect inhibition of TORC1 in presence of metformin, causes an increase in autophagy genes transcription, through overexpression and activation of transcription factor EB (TFEB), whose phospho-activation and nuclear translocation is TORC1-dependent. TFEB is a master regulator that controls essential processes in the life cycle of Echinococcus sp. as the endo-exocytosis (necessary in absence of digestive/excretory systems) and the biogenesis of autophagy key organelles as autophagosomes and lysosomes (given conditions of constant nutrient deficiency). Lastly, based on electron microscopy data, we showed that TFEB may induce ER-phagy in metformin-treated parasites, previous identification of ER specific receptors.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/250398
TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.; IX Congreso Argentino de Parasitología; Salta; Argentina; 2022; 94-94
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250398
identifier_str_mv TOR biology in Echinococcus sp.: Its roles in the cellular coordination of multiple metabolic and trafficking pathways… Huge and Powerful as Thor.; IX Congreso Argentino de Parasitología; Salta; Argentina; 2022; 94-94
CONICET Digital
CONICET
dc.language.none.fl_str_mv spa
language spa
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Asociación Parasitológica Argentina
publisher.none.fl_str_mv Asociación Parasitológica Argentina
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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