On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.

We have explored the mechanisms underlying ethanol-induced mitochondrial dynamics disruption and mitophagy. Ethanol increases mitochondrial fission in a concentration-dependent manner through Drp1 mitochondrial translocation and OPA1 proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial...

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Autores: Bonet Ponce, Luis, Sáez Atienzar, Sara, Da casa, Carmen, Flores Bellver, Miguel, Barcia, Jorge M., Sancho Pelluz, Javier, Romero, Francisco J., Jordán Bueso, Joaquín, Galindo Anaya, María Francisca
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/33369
Acceso en línea:https://hdl.handle.net/10578/33369
Access Level:acceso abierto
Palabra clave:Alcohol
Apoptosis
Bax
Drp-1
Oxidative stress
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repository_id_str
spelling On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.Bonet Ponce, LuisSáez Atienzar, SaraDa casa, CarmenFlores Bellver, MiguelBarcia, Jorge M. Sancho Pelluz, JavierRomero, Francisco J.Jordán Bueso, JoaquínGalindo Anaya, María FranciscaAlcoholApoptosisBaxDrp-1Oxidative stressWe have explored the mechanisms underlying ethanol-induced mitochondrial dynamics disruption and mitophagy. Ethanol increases mitochondrial fission in a concentration-dependent manner through Drp1 mitochondrial translocation and OPA1 proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial cell line) cells challenged with ethanol showed mitochondrial potential disruptions mediated by alterations in mitochondrial complex IV protein level and increases in mitochondrial reactive oxygen species production. In addition, ethanol activated the canonical autophagic pathway, as denoted by autophagosome formation and autophagy regulator elements including Beclin1, ATG5-ATG12 and P-S6 kinase. Likewise, autophagy inhibition dramatically increased mitochondrial fission and cell death, whereas autophagy stimulation rendered the opposite results, placing autophagy as a cytoprotective response aimed to remove damaged mitochondria. Interestingly, although ethanol induced mitochondrial Bax translocation, this episode was associated to cell death rather than mitochondrial fission or autophagy responses.Thus, Bax required 600 mM ethanol to migrate to mitochondria, a concentration that resulted in cell death. Furthermore, mouse embryonic fibroblasts lacking this protein respond to ethanol by undergoing mitochondrial fission and autophagy but not cytotoxicity. Finally, by using the specific mitochondrial-targeted scavenger MitoQ, we revealed mitochondria as the main source of reactive oxygen species that trigger autophagy activation. These findings suggest that cells respond to ethanol activating mitochondrial fission machinery by Drp1 and OPA1 rather than bax, in amanner that stimulates cytoprotective autophagy through mitochondrial ROS.Elsevier202420242015info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/33369reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésEMER07/023PI080693PI-2008/21PEII-2014-053-Pinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/333692026-05-27T07:36:41Z
dc.title.none.fl_str_mv On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
title On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
spellingShingle On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
Bonet Ponce, Luis
Alcohol
Apoptosis
Bax
Drp-1
Oxidative stress
title_short On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
title_full On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
title_fullStr On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
title_full_unstemmed On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
title_sort On the mechanism underlying ethanol-induced mitochondrial dynamic disruption and autophagy response.
dc.creator.none.fl_str_mv Bonet Ponce, Luis
Sáez Atienzar, Sara
Da casa, Carmen
Flores Bellver, Miguel
Barcia, Jorge M.
Sancho Pelluz, Javier
Romero, Francisco J.
Jordán Bueso, Joaquín
Galindo Anaya, María Francisca
author Bonet Ponce, Luis
author_facet Bonet Ponce, Luis
Sáez Atienzar, Sara
Da casa, Carmen
Flores Bellver, Miguel
Barcia, Jorge M.
Sancho Pelluz, Javier
Romero, Francisco J.
Jordán Bueso, Joaquín
Galindo Anaya, María Francisca
author_role author
author2 Sáez Atienzar, Sara
Da casa, Carmen
Flores Bellver, Miguel
Barcia, Jorge M.
Sancho Pelluz, Javier
Romero, Francisco J.
Jordán Bueso, Joaquín
Galindo Anaya, María Francisca
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alcohol
Apoptosis
Bax
Drp-1
Oxidative stress
topic Alcohol
Apoptosis
Bax
Drp-1
Oxidative stress
description We have explored the mechanisms underlying ethanol-induced mitochondrial dynamics disruption and mitophagy. Ethanol increases mitochondrial fission in a concentration-dependent manner through Drp1 mitochondrial translocation and OPA1 proteolytic cleavage. ARPE-19 (a human retinal pigment epithelial cell line) cells challenged with ethanol showed mitochondrial potential disruptions mediated by alterations in mitochondrial complex IV protein level and increases in mitochondrial reactive oxygen species production. In addition, ethanol activated the canonical autophagic pathway, as denoted by autophagosome formation and autophagy regulator elements including Beclin1, ATG5-ATG12 and P-S6 kinase. Likewise, autophagy inhibition dramatically increased mitochondrial fission and cell death, whereas autophagy stimulation rendered the opposite results, placing autophagy as a cytoprotective response aimed to remove damaged mitochondria. Interestingly, although ethanol induced mitochondrial Bax translocation, this episode was associated to cell death rather than mitochondrial fission or autophagy responses.Thus, Bax required 600 mM ethanol to migrate to mitochondria, a concentration that resulted in cell death. Furthermore, mouse embryonic fibroblasts lacking this protein respond to ethanol by undergoing mitochondrial fission and autophagy but not cytotoxicity. Finally, by using the specific mitochondrial-targeted scavenger MitoQ, we revealed mitochondria as the main source of reactive oxygen species that trigger autophagy activation. These findings suggest that cells respond to ethanol activating mitochondrial fission machinery by Drp1 and OPA1 rather than bax, in amanner that stimulates cytoprotective autophagy through mitochondrial ROS.
publishDate 2015
dc.date.none.fl_str_mv 2015
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/33369
url https://hdl.handle.net/10578/33369
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv EMER07/023
PI080693
PI-2008/21
PEII-2014-053-P
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419576754700288
score 15,300724

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