Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids

15 p.-6 fig.

Bibliographic Details
Authors: Swiader, Audrey, Nahapetyan, Hripsime, Faccini, Julien, D'Angelo, Romina, Mucher, Elodie, Elbaz, Meyer, Boya, Patricia, Vindis, Cécile
Format: article
Status:Published version
Publication Date:2016
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/134627
Online Access:http://hdl.handle.net/10261/134627
Access Level:Open access
Keyword:Human vascular smooth muscle cell
Mitophagy
Apoptosis
Oxidized lipoproteins
Atherosclerosis
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spelling Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipidsSwiader, AudreyNahapetyan, HripsimeFaccini, JulienD'Angelo, RominaMucher, ElodieElbaz, MeyerBoya, PatriciaVindis, CécileHuman vascular smooth muscle cellMitophagyApoptosisOxidized lipoproteinsAtherosclerosis15 p.-6 fig.Mitophagy is a critical cellular process that selectively targets damaged mitochondria for autophagosomal degradation both under baseline conditions and in response to stress preventing oxidative damage and cell death. Recent studies have linked alterations in mitochondria function and reduced autophagy with the development of age-related pathologies. However, the significance of mitochondrial autophagy in vessel wall in response to atherogenic lipid stressors is not known. In the present study, we investigated the role of mitophagy on human vascular smooth muscle cells (VSMC) apoptosis induced by oxidized low-density lipoproteins (LDL). We reported for the first time that the engulfment of defective mitochondria by autophagosomes occurred in human VSMC in response to oxidized LDL. The molecular mechanism mediating mitophagy in human VSMC involved dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, accumulation of PTEN-induced putative kinase 1 (PINK1) and the recruitment of the E3 ubiquitin ligase Parkin to mitochondria. Likewise, we found increased voltage-dependent anion channel 1 (VDAC1) and mitofusin 2 (Mnf2) mitochondrial proteins ubiquitination and LC3 association to mitochondria. Using flow cytometry in the presence of lysosomal inhibitors, we showed that PINK1 and Parkin silencing impaired mitophagy flux and enhanced oxidized LDL-induced VSMC apoptosis. In addition, overexpression of PINK1 and Parkin were protective by limiting cell death. Moreover, reduced Bax levels found in VSMC-overexpressing Parkin indicated cross talk among mitophagy and mitochondrial apoptotic signalling pathways. Altogether these data demonstrate that mitophagy is a safeguard mechanism against human VSMC apoptosis induced by atherogenic stressors and highlight mitophagy as a potential target to stabilize atherosclerotic plaque.This work was supported by grants from l’Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation de France [2013-38581 to C.V] and FU2015-64623-R to PB.Peer reviewedImpact JournalsInstitut National de la Santé et de la Recherche Médicale (France)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/134627reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/ 10.18632/oncotarget.8936Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1346272026-05-22T06:33:51Z
dc.title.none.fl_str_mv Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
title Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
spellingShingle Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
Swiader, Audrey
Human vascular smooth muscle cell
Mitophagy
Apoptosis
Oxidized lipoproteins
Atherosclerosis
title_short Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
title_full Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
title_fullStr Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
title_full_unstemmed Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
title_sort Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids
dc.creator.none.fl_str_mv Swiader, Audrey
Nahapetyan, Hripsime
Faccini, Julien
D'Angelo, Romina
Mucher, Elodie
Elbaz, Meyer
Boya, Patricia
Vindis, Cécile
author Swiader, Audrey
author_facet Swiader, Audrey
Nahapetyan, Hripsime
Faccini, Julien
D'Angelo, Romina
Mucher, Elodie
Elbaz, Meyer
Boya, Patricia
Vindis, Cécile
author_role author
author2 Nahapetyan, Hripsime
Faccini, Julien
D'Angelo, Romina
Mucher, Elodie
Elbaz, Meyer
Boya, Patricia
Vindis, Cécile
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut National de la Santé et de la Recherche Médicale (France)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Human vascular smooth muscle cell
Mitophagy
Apoptosis
Oxidized lipoproteins
Atherosclerosis
topic Human vascular smooth muscle cell
Mitophagy
Apoptosis
Oxidized lipoproteins
Atherosclerosis
description 15 p.-6 fig.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/134627
url http://hdl.handle.net/10261/134627
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/ 10.18632/oncotarget.8936
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411454346592256
score 15,811543

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