Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spira...

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Autores: Bustillo Zabalbeitia, Itsasne, Montessuit, Sylvie, Raemy, Etienne, Basáñez Asúa, Gorka, Terrones Urio, Oihana, Martinou, Jean-Claude
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/16405
Acceso en línea:http://hdl.handle.net/10810/16405
Access Level:acceso abierto
Palabra clave:dominant optic atrophy
mitochondrial fission
oxidative-phosphorylation
conformational-changes
menbrane-binding
mammalian cells
DRP1
GTPase
fusion
domain
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
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oai_identifier_str oai:addi.ehu.eus:10810/16405
network_acronym_str ES
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repository_id_str
spelling Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1Bustillo Zabalbeitia, ItsasneMontessuit, SylvieRaemy, EtienneBasáñez Asúa, GorkaTerrones Urio, OihanaMartinou, Jean-Claudedominant optic atrophymitochondrial fissionoxidative-phosphorylationconformational-changesmenbrane-bindingmammalian cellsDRP1GTPasefusiondomainAGRICULTURAL AND BIOLOGICAL SCIENCESMEDICINEBIOCHEMISTRY AND MOLECULAR BIOLOGYDynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.This work was funded by the Swiss National Science Foundation (31993A-141068/1), IGE3 and the State of Geneva (J.-C.M.), the Spanish Ministerio de Ciencia e Innovacion grant BFU2011-28566 and the Basque Government grant IT838-13 (G.B., O.T.). O.T. was supported by a postdoctoral Juan de la Cierva fellow, Spanish Government, and by a FEBS Short-Term fellowship. I.B.-Z. was supported by a predoctoral fellowship from the Basque Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library Science201520152014info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/16405reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/BFU2011-28566/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102738#abstract0info:eu-repo/semantics/openAccess2014 Bustillo-Zabalbeitia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.oai:addi.ehu.eus:10810/164052026-06-18T09:23:17Z
dc.title.none.fl_str_mv Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
title Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
spellingShingle Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
Bustillo Zabalbeitia, Itsasne
dominant optic atrophy
mitochondrial fission
oxidative-phosphorylation
conformational-changes
menbrane-binding
mammalian cells
DRP1
GTPase
fusion
domain
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
title_short Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
title_full Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
title_fullStr Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
title_full_unstemmed Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
title_sort Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1
dc.creator.none.fl_str_mv Bustillo Zabalbeitia, Itsasne
Montessuit, Sylvie
Raemy, Etienne
Basáñez Asúa, Gorka
Terrones Urio, Oihana
Martinou, Jean-Claude
author Bustillo Zabalbeitia, Itsasne
author_facet Bustillo Zabalbeitia, Itsasne
Montessuit, Sylvie
Raemy, Etienne
Basáñez Asúa, Gorka
Terrones Urio, Oihana
Martinou, Jean-Claude
author_role author
author2 Montessuit, Sylvie
Raemy, Etienne
Basáñez Asúa, Gorka
Terrones Urio, Oihana
Martinou, Jean-Claude
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv dominant optic atrophy
mitochondrial fission
oxidative-phosphorylation
conformational-changes
menbrane-binding
mammalian cells
DRP1
GTPase
fusion
domain
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
topic dominant optic atrophy
mitochondrial fission
oxidative-phosphorylation
conformational-changes
menbrane-binding
mammalian cells
DRP1
GTPase
fusion
domain
AGRICULTURAL AND BIOLOGICAL SCIENCES
MEDICINE
BIOCHEMISTRY AND MOLECULAR BIOLOGY
description Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.
publishDate 2014
dc.date.none.fl_str_mv 2014
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/16405
url http://hdl.handle.net/10810/16405
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/BFU2011-28566/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102738#abstract0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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