EMC3 loss disrupts triglyceride storage in mice and flies

A team from the Gulbenkian Institute for Molecular Medicine and ITQB NOVA (Oeiras, Portugal), the University of Oxford and Queen's University Belfast reported in Nature Communications, published on 3 November 2026, that the ER membrane complex (EMC) is needed for normal triglyceride storage in mice and in Drosophila. doi.org The EMC inserts integral membrane proteins into the lipid bilayer of the endoplasmic reticulum (ER). doi.org Its structure has been studied in detail in recent years, but which proteins depend on it and what it does across evolution remained less well understood, the authors write. doi.org

Tissue-specific EMC3 deletion in mice

The researchers deleted the essential EMC3 subunit in the liver and in adipose tissues of mice. They then examined the animals in a range of metabolic and lipid homeostasis models. doi.org

Loss of EMC3 in either the liver or adipose tissue led to defective storage of triglycerides and disturbed lipid droplet (LD) homeostasis. doi.org Adipose tissue lacking EMC was less able to mediate fat storage in mice on a high-fat diet. It was also unable to support non-shivering thermogenesis. doi.org

FITM2 as an EMC client

Proteomic analysis of EMC3-deficient tissues showed reduced levels of FITM2, a key regulator of LD biogenesis and ER homeostasis. On this basis the authors identify FITM2 as an EMC client. doi.org

The team then deleted EMC3 in the fat body of Drosophila, which produced similar defects in LD homeostasis. These defects were rescued by a FITM2 mutant whose biogenesis does not depend on the EMC. doi.org

The authors conclude that the EMC plays a key, evolutionarily conserved role in the biogenesis of the machinery that maintains triglyceride storage in metazoans. doi.org The data come from mouse and fly models. The corresponding authors are John C. Christianson, Pedro M. Domingos and Colin Adrain. doi.org

EMC3 deletion in mouse liver and fat impairs triglyceride storage; FITM2 identified as EMC client

Tissue-specific EMC3 deletion in mice

FITM2 as an EMC client

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