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

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Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results A critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis Erika de Carvalho , Abdulbasit Amin , Richard LiIttle , Keily Fonseca Silva , Catarina Gaspar , Marina Badenes , Emma Burbridge , Tiago Paixao , Maria Joao Amorim , Pedro Faisca , View ORCID Profile Roman Fischer , Iolanda Vendrell , View ORCID Profile Darragh P O'Brien , View ORCID Profile Kvido Strisovsky , View ORCID Profile John C Christianson , View ORCID Profile Pedro Domingos , Colin Adrain doi: https://doi.org/10.1101/2025.03.10.642408 Erika de Carvalho 1 Gulbenkian Institute for Molecular Medicine, Oeiras, Portugal.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abdulbasit Amin 2 Gulbenkian Institute for Molecular Medicine, Oeiras, Portugal; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Richard LiIttle 3 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Keily Fonseca Silva 4 Instituto de Tecnologia Quimica e Biologica Antonio Xavier, Universidade Nova de Lisboa, Oeiras, Portugal; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Catarina Gaspar 5 Cancer Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marina Badenes 6 Faculty of Veterinary Medicine, Lusofona University, Lisbon, Portugal; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Emma Burbridge 7 Patrick G Johnston Centre for Cancer Research, Queens University Belfast, N. Ireland.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tiago Paixao 1 Gulbenkian Institute for Molecular Medicine, Oeiras, Portugal.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Maria Joao Amorim 8 Catolica Biomedical Research Center, Faculty of Medicine of the Universidade Catolica Portuguesa, Oeiras, Portugal; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pedro Faisca 1 Gulbenkian Institute for Molecular Medicine, Oeiras, Portugal.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Roman Fischer 9 University of Oxford; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Roman Fischer Iolanda Vendrell 9 University of Oxford; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Darragh P O'Brien 9 University of Oxford; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Darragh P O'Brien Kvido Strisovsky 10 Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic.; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kvido Strisovsky John C Christianson 9 University of Oxford; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for John C Christianson Pedro Domingos 11 ITQB-UNL; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Pedro Domingos Colin Adrain 12 Queen's University Belfast Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: c.adrain{at}qub.ac.uk Abstract Info/History Metrics Supplementary material Preview PDF Abstract The 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. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license . View the discussion thread. Back to top Previous Next Posted March 13, 2025. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share A critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis Erika de Carvalho , Abdulbasit Amin , Richard LiIttle , Keily Fonseca Silva , Catarina Gaspar , Marina Badenes , Emma Burbridge , Tiago Paixao , Maria Joao Amorim , Pedro Faisca , Roman Fischer , Iolanda Vendrell , Darragh P O'Brien , Kvido Strisovsky , John C Christianson , Pedro Domingos , Colin Adrain bioRxiv 2025.03.10.642408; doi: https://doi.org/10.1101/2025.03.10.642408 Share This Article: Copy Citation Tools A critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis Erika de Carvalho , Abdulbasit Amin , Richard LiIttle , Keily Fonseca Silva , Catarina Gaspar , Marina Badenes , Emma Burbridge , Tiago Paixao , Maria Joao Amorim , Pedro Faisca , Roman Fischer , Iolanda Vendrell , Darragh P O'Brien , Kvido Strisovsky , John C Christianson , Pedro Domingos , Colin Adrain bioRxiv 2025.03.10.642408; doi: https://doi.org/10.1101/2025.03.10.642408 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Biochemistry Subject Areas All Articles Animal Behavior and Cognition (7637) Biochemistry (17705) Bioengineering (13899) Bioinformatics (41968) Biophysics (21460) Cancer Biology (18603) Cell Biology (25526) Clinical Trials (138) Developmental Biology (13385) Ecology (19910) Epidemiology (2067) Evolutionary Biology (24328) Genetics (15614) Genomics (22513) Immunology (17741) Microbiology (40423) Molecular Biology (17193) Neuroscience (88646) Paleontology (667) Pathology (2835) Pharmacology and Toxicology (4827) Physiology (7647) Plant Biology (15160) Scientific Communication and Education (2046) Synthetic Biology (4302) Systems Biology (9825) Zoology (2271)