Retrograde Golgi-to-ER transport is regulated by diacylglycerol in <i>Saccharomyces cerevisiae</i>

Coat protein complex (COP) I (COPI)-mediated retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER) plays a crucial role not only in recycling mislocalized and/or misfolded proteins to the ER but also in maintaining ER and Golgi structure and function. This pathway is tightly coordinated with COPII-mediated anterograde transport to ensure cellular homeostasis. In the regulation of bidirectional vesicular trafficking, lipids act as indispensable structural components of vesicles. Among these, the cone-shaped lipid diacylglycerol (DAG) has long been known to be involved in COPI function in mammalian cells. However, whether this regulatory mechanism is conserved across species remains unknown. In this study, we identify diacylglycerol (DAG) as a key modulator of COPI-mediated retrograde transport in budding yeast, demonstrating that DAG accumulation rescues both lethality and transport defects in COPI retrieval mutants. Notably, DAG levels decrease upon inhibition of retrograde transport and increase upon its restoration. These findings suggest that DAG regulates retrograde transport in a manner that promotes COPI vesicle formation, underscoring its potential role as a lipid mediator in cellular trafficking.