Logo do repositório
 
Publicação

A critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis

2025-03-11Preprint Acesso aberto
Ver registo simples
dc.contributor.authorCarvalho, Érika de
dc.contributor.authorAmin, Abdulbasit
dc.contributor.authorLittle, Richard
dc.contributor.authorSilva, Keily Fonseca
dc.contributor.authorGaspar, Catarina
dc.contributor.authorBadenes, Marina
dc.contributor.authorBurbridge, Emma
dc.contributor.authorPaixão, Tiago
dc.contributor.authorAmorim, Maria João
dc.contributor.authorFaísca, Pedro
dc.contributor.authorFischer, Roman
dc.contributor.authorVendrel, Iolanda
dc.contributor.authorO’Brien, Darragh P.
dc.contributor.authorStrisovsky, Kvido
dc.contributor.authorChristianson, John C.
dc.contributor.authorDomingos, Pedro M.
dc.contributor.authorAdrain, Colin
dc.date.accessioned2026-08-03T15:25:46Z
dc.date.available2026-08-03T15:25:46Z
dc.date.issued2025-03-11
dc.description.abstractThe ER Membrane complex (EMC) facilitates insertion of multiple classes of integral membrane protein into the lipid bilayer of the endoplasmic reticulum (ER). Recent years have seen significant progress in understanding the structural aspects of EMC function, but the client protein/s enforcing its evolutionary conservation throughout eukaryotic kingdoms remain to be determined. Given reported role/s for the EMC in lipid homeostasis, we deleted the essential EMC3 subunit in the liver and adipose tissues of mice and examined the impact of EMC loss in a range of metabolic models. Intriguingly, absence of EMC3 in either the liver or adipose tissues results in defective storage of triglycerides and perturbations in lipid droplet (LD) homeostasis. EMC-deficient mouse adipose tissues were defective in their ability to mediate fat storage in response to a high fat diet and were unable to support non-shivering thermogenesis. Proteomic analyses of EMC3-deficient tissues found reduced levels of FITM2, a key regulator of LD biogenesis and ER homeostasis, identifying it as a novel EMC client. Strikingly, deletion of the EMC3 homolog dPob in the Drosophila fat body, which shares overlapping functions with mammalian liver/adipose tissues, revealed similar defects in LD homeostasis. Together, our results indicate that the EMC plays a key evolutionarily conserved role in biogenesis of machinery maintaining triglyceride storage in metazoans.eng
dc.identifier.doi10.1101/2025.03.10.642408
dc.identifier.other197f1b5f-8213-4230-8db9-a36ed4f81c05
dc.identifier.urihttp://hdl.handle.net/10400.14/59009
dc.language.isoeng
dc.publisherbioRxiv
dc.rights.uriN/A
dc.titleA critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis
dc.typepreprint
dspace.entity.typePublication
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
156794725.pdf
Tamanho:
10.78 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

CBR - Working Papers / Preprints