Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis

The EMC complex, a highly conserved transmembrane chaperone in the endoplasmic reticulum (ER), has been associated in humans with sterol homeostasis and a myriad of different cellular activities, rendering the mechanism of EMC functionality enigmatic. Using fission yeast, we demonstrate that the EMC...

Descripción completa

Detalles Bibliográficos
Autores: Berraquero, Modesto, Álvarez Tallada, Víctor, Jiménez, Juan
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Pablo de Olavide (UPO)
Repositorio:RIO. Repositorio Institucional Olavide
Idioma:inglés
OAI Identifier:oai:rio.upo.es:10433/26092
Acceso en línea:https://hdl.handle.net/10433/26092
Access Level:acceso abierto
Palabra clave:Biochemistry
Cell biology
Molecular biology
id ES_652c587147e3c1af69c19cf0ac444bf7
oai_identifier_str oai:rio.upo.es:10433/26092
network_acronym_str ES
network_name_str España
repository_id_str
spelling Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesisBerraquero, ModestoÁlvarez Tallada, VíctorJiménez, JuanBiochemistryCell biologyMolecular biologyThe EMC complex, a highly conserved transmembrane chaperone in the endoplasmic reticulum (ER), has been associated in humans with sterol homeostasis and a myriad of different cellular activities, rendering the mechanism of EMC functionality enigmatic. Using fission yeast, we demonstrate that the EMC complex facilitates the biogenesis of the sterol transfer protein Lam6/Ltc1 at ER-plasma membrane and ER-mitochondria contact sites. Cells that lose EMC function sequester unfolded Lam6/Ltc1 and other proteins at the mitochondrial matrix, leading to surplus ergosterol, cold-sensitive growth, and mitochondrial dysfunctions. Remarkably, inhibition of ergosterol biosynthesis, but also fluidization of cell membranes to counteract their rigidizing effects, reduce the ER-unfolded protein response and rescue growth and mitochondrial defects in EMC-deficient cells. These results suggest that EMC-assisted biogenesis of Lam6/Ltc1 may provide, through ergosterol homeostasis, optimal membrane fluidity to facilitate biogenesis of other ER-membrane proteins.Elsevier Inc. Cell Press20262026-02-1120252025-03-2120252025-03-21journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10433/26092reponame:RIO. Repositorio Institucional Olavideinstname:Universidad Pablo de Olavide (UPO)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:rio.upo.es:10433/260922026-06-13T12:46:27Z
dc.title.none.fl_str_mv Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
title Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
spellingShingle Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
Berraquero, Modesto
Biochemistry
Cell biology
Molecular biology
title_short Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
title_full Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
title_fullStr Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
title_full_unstemmed Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
title_sort Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
dc.creator.none.fl_str_mv Berraquero, Modesto
Álvarez Tallada, Víctor
Jiménez, Juan
author Berraquero, Modesto
author_facet Berraquero, Modesto
Álvarez Tallada, Víctor
Jiménez, Juan
author_role author
author2 Álvarez Tallada, Víctor
Jiménez, Juan
author2_role author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Biochemistry
Cell biology
Molecular biology
topic Biochemistry
Cell biology
Molecular biology
description The EMC complex, a highly conserved transmembrane chaperone in the endoplasmic reticulum (ER), has been associated in humans with sterol homeostasis and a myriad of different cellular activities, rendering the mechanism of EMC functionality enigmatic. Using fission yeast, we demonstrate that the EMC complex facilitates the biogenesis of the sterol transfer protein Lam6/Ltc1 at ER-plasma membrane and ER-mitochondria contact sites. Cells that lose EMC function sequester unfolded Lam6/Ltc1 and other proteins at the mitochondrial matrix, leading to surplus ergosterol, cold-sensitive growth, and mitochondrial dysfunctions. Remarkably, inhibition of ergosterol biosynthesis, but also fluidization of cell membranes to counteract their rigidizing effects, reduce the ER-unfolded protein response and rescue growth and mitochondrial defects in EMC-deficient cells. These results suggest that EMC-assisted biogenesis of Lam6/Ltc1 may provide, through ergosterol homeostasis, optimal membrane fluidity to facilitate biogenesis of other ER-membrane proteins.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-03-21
2025
2025-03-21
2026
2026-02-11
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10433/26092
url https://hdl.handle.net/10433/26092
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc. Cell Press
publisher.none.fl_str_mv Elsevier Inc. Cell Press
dc.source.none.fl_str_mv reponame:RIO. Repositorio Institucional Olavide
instname:Universidad Pablo de Olavide (UPO)
instname_str Universidad Pablo de Olavide (UPO)
reponame_str RIO. Repositorio Institucional Olavide
collection RIO. Repositorio Institucional Olavide
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869409722347552768
score 15,81155

Similares en LA Referencia