LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs
dc.contributor.author | Iriondo Nagore, Marina | |
dc.contributor.author | Etxaniz Iriondo, Asier | |
dc.contributor.author | Varela Fernández, Yaiza | |
dc.contributor.author | Ballesteros Rivero, Uxue | |
dc.contributor.author | Hervás Hidalgo, Javier ![]() | |
dc.contributor.author | Montes Burgos, Lidia Ruth ![]() | |
dc.contributor.author | Goñi Urcelay, Félix María ![]() | |
dc.contributor.author | Alonso Izquierdo, Alicia ![]() | |
dc.date.accessioned | 2023-02-09T17:17:25Z | |
dc.date.available | 2023-02-09T17:17:25Z | |
dc.date.issued | 2022-12 | |
dc.identifier.citation | Autophagy 18(12) : 2985-3003 (2022) | es_ES |
dc.identifier.issn | 1554-8627 | |
dc.identifier.issn | 1554-8635 | |
dc.identifier.uri | http://hdl.handle.net/10810/59740 | |
dc.description.abstract | Externalization of the phospholipid cardiolipin (CL) to the outer mitochondrial membrane has been proposed to act as a mitophagy trigger. CL would act as a signal for binding the LC3 macroauto-phagy/autophagy proteins. As yet, the behavior of the LC3-subfamily members has not been directly compared in a detailed way. In the present contribution, an analysis of LC3A, LC3B and LC3C interaction with CL-containing model membranes, and of their ability to translocate to mitochondria, is described. Binding of LC3A to CL was stronger than that of LC3B; both proteins showed a similar ability to colocalize with mitochondria upon induction of CL externalization in SH-SY5Y cells. Besides, the double silencing of LC3A and LC3B proteins was seen to decrease CCCP-induced mitophagy. Residues 14 and 18 located in the N-terminal region of LC3A were shown to be important for its recognition of damaged mitochondria during rotenone- or CCCP-induced mitophagy. Moreover, the in vitro results suggested a possible role of LC3A, but not of LC3B, in oxidized-CL recognition as a counterweight to excessive apoptosis activation. In the case of LC3C, even if this protein showed a stronger CL binding than LC3B or LC3A, the interaction was less specific, and colocalization of LC3C with mitochondria was not rotenone dependent. These results suggest that, at variance with LC3A, LC3C does not participate in cargo recognition during CL-mediated-mitophagy. The data support the notion that the various LC3-subfamily members might play different roles during autophagy initia-tion, identifying LC3A as a novel stakeholder in CL-mediated mitophagy. | es_ES |
dc.description.sponsorship | This work was supported in part by the Spanish Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (grant No. PGC2018-099857- B-I00), by the Basque Government (grants No. IT1625-22 and IT1270- 19), by Fundación Ramón Areces (CIVP20A6619), by Fundación Biofísica Bizkaia and by the Basque Excellence Research Centre (BERC) program of the Basque Government. MI and YV were recipients of predoctoral FPU fellowships from the Spanish Ministry of Science Innovation and Universities (FPU16/05873, FPU18/00799), UB thanks the University of the Basque Country for a predoctoral contract, JHH was supported by a Postdoctoral Fellowship from the Basque Government. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Taylor & Francis | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/PGC2018-099857-B-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Atg8 | es_ES |
dc.subject | autophagosome | es_ES |
dc.subject | autophagy cargo recognition | es_ES |
dc.subject | LC3/GABARAP- protein family | es_ES |
dc.subject | lipid oxidation | es_ES |
dc.subject | lipid-protein interaction | es_ES |
dc.subject | membrane curvature | es_ES |
dc.subject | mitochondria | es_ES |
dc.subject | negatively charged phospholipids | es_ES |
dc.title | LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.tandfonline.com/doi/full/10.1080/15548627.2022.2062111 | es_ES |
dc.identifier.doi | 10.1080/15548627.2022.2062111 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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Except where otherwise noted, this item's license is described as © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.