Csf1 facilitates adaptive membrane lipid remodeling linked to ER-plasma membrane contact sites.

Membrane lipid composition must be dynamically adjusted to preserve bilayer physical properties, yet the cellular mechanisms that support bulk lipid remodeling under physical stress remain incompletely understood. Here, we identify Csf1 as a regulator of membrane lipid remodeling functionally associated with endoplasmic reticulum-plasma membrane (ER-PM) contact sites in Saccharomyces cerevisiae, with features consistent with bridge-like lipid transfer proteins. Using high hydrostatic pressure as a defined physical perturbation that constrains membrane packing, we reveal a requirement for Csf1-dependent lipid remodeling linked to ER-PM contact sites that is masked under standard growth conditions. Quantitative lipidomic and membrane biophysical analyses show that, under hydrostatic compression, loss of Csf1 disrupts coordinated lipid remodeling, leading to reduced phospholipid unsaturation, increased membrane rigidity, and destabilization of PM permeases. We further show that Csf1 cooperates with Osh6/7 to sustain lipid flux and bilayer re-equilibration linked to ER-PM contact sites under conditions permissive for Osh6/7 activity. These findings identify Csf1 as a stress-dependent lipid-remodeling factor that enables adaptive membrane remodeling and preserves membrane protein stability under conditions of constrained membrane flexibility.