Quality control at the Golgi couples membrane proteostasis to lipid metabolism

Loss of a Golgi quality control checkpoint in budding yeast causes persistent accumulation and mislocalization of membrane clients, including lipid-regulating proteins, leading to diacylglycerol-enriched multilamellar compartment buildup.

• Why it matters: Secretory-pathway QC is mainly attributed to the ER, leaving whether the Golgi also safeguards membrane proteostasis and lipid composition unclear.
• What they did: Genome-wide screens in budding yeast identified a two-branch system where Rer1 retrieves transient orphan/mislocalized clients to the ER and the Dsc complex ubiquitinates terminal clients for degradation based on transmembrane domains.
• The result: Checkpoint loss scrambles compartment composition and deregulates lipid metabolism, progressively collapsing cellular architecture; draining excess diacylglycerol dissolves DMCs and largely restores architecture and viability, while the proteostasis defect persists.