Retromer mediates Ypt7-dependent lipid droplet internalization

This is the authors' abstract. We don't add key points for this paper.

Lipid droplets (LDs) are dynamic organelles central to cellular energy homeostasis and stress adaptation. Maintaining LD balance is critical for cell function, yet the mechanisms governing selective LD degradation remain unclear. Here, we reveal a pathway promoting efficient vacuolar sequestering and potential degradation of a Pdr16-marked LD subpopulation, thereby linking LD metabolism to organelle communication. During nutrient limitation, the Rab GTPase Ypt7 and its guanine nucleotide exchange factor (GEF), Mon1-Ccz1, specifically localize to Pdr16-LDs. This targeting relies on a conserved amphipathic helix within Ccz1. Importantly, Ypt7 activation recruits the SNX-BAR retromer complex to the vacuole-LD interface at sites of invagination. There, retromer potentially interacts with its cargo receptor, Vps10, to promote positive membrane curvature that drives the late stage of vacuolar invagination required for LD internalization and degradation. These findings suggest a link between LD turnover, organelle interactions, and cellular adaptation to metabolic stress, providing new insight into lipid homeostasis.