A critical role for the ER Membrane Complex (EMC) in lipid droplet homeostasis
de Carvalho, E.; Amin, A.; LiIttle, R.; Silva, K. F.; Gaspar, C.; Badenes, M.; Burbridge, E.; Paixao, T.; Amorim, M. J.; Faisca, P.; Fischer, R.; Vendrell, I.; O'Brien, D. P.; Strisovsky, K.; Christianson, J. C.; Domingos, P.; Adrain, C.
Show 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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Active integrins regulate white adipose tissue insulin sensitivity and brown fat thermogenesis 97%
- Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis 96%
- The Diabetes Gene Tcf7l2 Organizes Gene Expression in the Liver and Regulates Amino Acid Metabolism 96%
Similar papers in this journal
- A mouse model of human mitofusin 2-related lipodystrophy exhibits adipose-specific mitochondrial stress and reduced leptin secretion 97%
- Control of brown adipose tissue adaptation to nutrient stress by the activin receptor ALK7 96%
- Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease 96%
Similar papers in this journal
- Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. 96%
- Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue 96%
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria 96%
Similar papers in this journal
- Divergent roles for caspase-8 and MLKL in high-fat diet induced obesity and NAFLD in mice 97%
- Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction in C9orf72 ALS/FTD in vivo models and patient iNeurons 94%
- An integrated stress response-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.