Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids

Autores
Peñalva, Daniel Alejandro; Monnappa, Ajay K.; Natale, Paolo; López Montero, Iván
Año de publicación
2022
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Membrane fusion is crucial for the coordination of mitochondrial dynamics. an imbalanced mitochondrial dynamic leads to the formation of fragmented mitochondria and a decrease in intracellular atp levels, contributing to the development of important diseases, including neurodegenerative, cardiac or cancer conditions. the fusion process is energetically unfavorable, thereby requiring specialized proteins. in mammals, mitofusins (mfn) 1 and 2 are responsible for mitochondrial outer-membrane (omm) fusion. they belong to the dynamin superfamily of multi-domain gtpases. recent structural studies suggest that, upon gtp hydrolysis, mfns dimerize to promote the approaching and fusion of omm. however, the omm fusion seems to require multiple regulatory factors that control the dynamics and kinetics of mitochondrial fusion throught the formation of heterotypic mfn1- mfn2 dimers. in this study, we purified and functionally reconstituted the full-length mouse mfn2 in large and giant unilamellar vesicles (luvs and guvs, respectively). vesicles were prepared with popc alone or with 30% of plasmalogen-pc or dope. unlike gdp, after incubation with gtp, vesicles underwent fusion. fast video microscopy imaged the mfn2-dependent membrane fusion pathway which involves the formation and expansion of a membrane diaphragm and the opening of a fusion pore. the incorporation of dope (30% mol) in the lipid composition did not alter the fusion sequence but enhanced the fusion kinetics significantly, as revealed by a lipid-mixing assay. our observations show that mfn2 alone can promote the fusion of micron-sized vesicles, without the presence of other proteins in the membrane. in addition, the lipid environment is an important factor in the modulation of mfn2-dependent membrane fusion, a process that seems to require topological lipid intermediates with negative curvature
Fil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Monnappa, Ajay K.. Hospital Doce de Octubre; España
Fil: Natale, Paolo. Hospital Doce de Octubre; España. Universidad Complutense de Madrid; España
Fil: López Montero, Iván. Universidad Complutense de Madrid; España
LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
Materia
MITOFUSIN
MEMBRANE FUSION
MITOCHONDRIA
LIPID VESICLES
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:11336/201610
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/201610
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipidsPeñalva, Daniel AlejandroMonnappa, Ajay K.Natale, PaoloLópez Montero, IvánMITOFUSINMEMBRANE FUSIONMITOCHONDRIALIPID VESICLEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Membrane fusion is crucial for the coordination of mitochondrial dynamics. an imbalanced mitochondrial dynamic leads to the formation of fragmented mitochondria and a decrease in intracellular atp levels, contributing to the development of important diseases, including neurodegenerative, cardiac or cancer conditions. the fusion process is energetically unfavorable, thereby requiring specialized proteins. in mammals, mitofusins (mfn) 1 and 2 are responsible for mitochondrial outer-membrane (omm) fusion. they belong to the dynamin superfamily of multi-domain gtpases. recent structural studies suggest that, upon gtp hydrolysis, mfns dimerize to promote the approaching and fusion of omm. however, the omm fusion seems to require multiple regulatory factors that control the dynamics and kinetics of mitochondrial fusion throught the formation of heterotypic mfn1- mfn2 dimers. in this study, we purified and functionally reconstituted the full-length mouse mfn2 in large and giant unilamellar vesicles (luvs and guvs, respectively). vesicles were prepared with popc alone or with 30% of plasmalogen-pc or dope. unlike gdp, after incubation with gtp, vesicles underwent fusion. fast video microscopy imaged the mfn2-dependent membrane fusion pathway which involves the formation and expansion of a membrane diaphragm and the opening of a fusion pore. the incorporation of dope (30% mol) in the lipid composition did not alter the fusion sequence but enhanced the fusion kinetics significantly, as revealed by a lipid-mixing assay. our observations show that mfn2 alone can promote the fusion of micron-sized vesicles, without the presence of other proteins in the membrane. in addition, the lipid environment is an important factor in the modulation of mfn2-dependent membrane fusion, a process that seems to require topological lipid intermediates with negative curvatureFil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Monnappa, Ajay K.. Hospital Doce de Octubre; EspañaFil: Natale, Paolo. Hospital Doce de Octubre; España. Universidad Complutense de Madrid; EspañaFil: López Montero, Iván. Universidad Complutense de Madrid; EspañaLVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology ResearchArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularSociedad Argentina de Investigaciones en Bioquimica y Biología Molecular2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/201610Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Argentina; 2022; 84-84CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://newsite.saib.org.ar/congreso2022/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:00Zoai:ri.conicet.gov.ar:11336/201610instacron: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 10:00:00.531CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
title Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
spellingShingle Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
Peñalva, Daniel Alejandro
MITOFUSIN
MEMBRANE FUSION
MITOCHONDRIA
LIPID VESICLES
title_short Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
title_full Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
title_fullStr Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
title_full_unstemmed Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
title_sort Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids
dc.creator.none.fl_str_mv Peñalva, Daniel Alejandro
Monnappa, Ajay K.
Natale, Paolo
López Montero, Iván
author Peñalva, Daniel Alejandro
author_facet Peñalva, Daniel Alejandro
Monnappa, Ajay K.
Natale, Paolo
López Montero, Iván
author_role author
author2 Monnappa, Ajay K.
Natale, Paolo
López Montero, Iván
author2_role author
author
author
dc.subject.none.fl_str_mv MITOFUSIN
MEMBRANE FUSION
MITOCHONDRIA
LIPID VESICLES
topic MITOFUSIN
MEMBRANE FUSION
MITOCHONDRIA
LIPID VESICLES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Membrane fusion is crucial for the coordination of mitochondrial dynamics. an imbalanced mitochondrial dynamic leads to the formation of fragmented mitochondria and a decrease in intracellular atp levels, contributing to the development of important diseases, including neurodegenerative, cardiac or cancer conditions. the fusion process is energetically unfavorable, thereby requiring specialized proteins. in mammals, mitofusins (mfn) 1 and 2 are responsible for mitochondrial outer-membrane (omm) fusion. they belong to the dynamin superfamily of multi-domain gtpases. recent structural studies suggest that, upon gtp hydrolysis, mfns dimerize to promote the approaching and fusion of omm. however, the omm fusion seems to require multiple regulatory factors that control the dynamics and kinetics of mitochondrial fusion throught the formation of heterotypic mfn1- mfn2 dimers. in this study, we purified and functionally reconstituted the full-length mouse mfn2 in large and giant unilamellar vesicles (luvs and guvs, respectively). vesicles were prepared with popc alone or with 30% of plasmalogen-pc or dope. unlike gdp, after incubation with gtp, vesicles underwent fusion. fast video microscopy imaged the mfn2-dependent membrane fusion pathway which involves the formation and expansion of a membrane diaphragm and the opening of a fusion pore. the incorporation of dope (30% mol) in the lipid composition did not alter the fusion sequence but enhanced the fusion kinetics significantly, as revealed by a lipid-mixing assay. our observations show that mfn2 alone can promote the fusion of micron-sized vesicles, without the presence of other proteins in the membrane. in addition, the lipid environment is an important factor in the modulation of mfn2-dependent membrane fusion, a process that seems to require topological lipid intermediates with negative curvature
Fil: Peñalva, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Monnappa, Ajay K.. Hospital Doce de Octubre; España
Fil: Natale, Paolo. Hospital Doce de Octubre; España. Universidad Complutense de Madrid; España
Fil: López Montero, Iván. Universidad Complutense de Madrid; España
LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research
Argentina
Sociedad Argentina de Investigación Bioquímica y Biología Molecular
description Membrane fusion is crucial for the coordination of mitochondrial dynamics. an imbalanced mitochondrial dynamic leads to the formation of fragmented mitochondria and a decrease in intracellular atp levels, contributing to the development of important diseases, including neurodegenerative, cardiac or cancer conditions. the fusion process is energetically unfavorable, thereby requiring specialized proteins. in mammals, mitofusins (mfn) 1 and 2 are responsible for mitochondrial outer-membrane (omm) fusion. they belong to the dynamin superfamily of multi-domain gtpases. recent structural studies suggest that, upon gtp hydrolysis, mfns dimerize to promote the approaching and fusion of omm. however, the omm fusion seems to require multiple regulatory factors that control the dynamics and kinetics of mitochondrial fusion throught the formation of heterotypic mfn1- mfn2 dimers. in this study, we purified and functionally reconstituted the full-length mouse mfn2 in large and giant unilamellar vesicles (luvs and guvs, respectively). vesicles were prepared with popc alone or with 30% of plasmalogen-pc or dope. unlike gdp, after incubation with gtp, vesicles underwent fusion. fast video microscopy imaged the mfn2-dependent membrane fusion pathway which involves the formation and expansion of a membrane diaphragm and the opening of a fusion pore. the incorporation of dope (30% mol) in the lipid composition did not alter the fusion sequence but enhanced the fusion kinetics significantly, as revealed by a lipid-mixing assay. our observations show that mfn2 alone can promote the fusion of micron-sized vesicles, without the presence of other proteins in the membrane. in addition, the lipid environment is an important factor in the modulation of mfn2-dependent membrane fusion, a process that seems to require topological lipid intermediates with negative curvature
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
Book
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/11336/201610
Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Argentina; 2022; 84-84
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201610
identifier_str_mv Fusion of micron-size vesicles: interplay between the mitochondrial Mfn2 protein and lipids; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Argentina; 2022; 84-84
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://newsite.saib.org.ar/congreso2022/
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 Sociedad Argentina de Investigaciones en Bioquimica y Biología Molecular
publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquimica y Biología Molecular
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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score 13.070432

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