A dynamic feedback loop between retrograde sterol transport and TORC2 controls adaptation of the plasma membrane to stress.

ABSTRACT: Cells monitor and dynamically regulate the lipid composition and biophysical properties of their plasma membrane (PM). The Target Of Rapamycin complex 2 (TORC2) is a protein kinase that acts as a central regulator of plasma membrane homeostasis, but the mechanisms by which it detects and reacts to membrane stresses are poorly understood. To address this knowledge gap, we characterized a family of amphiphilic molecules that physically perturb plasma membrane organization and in doing so inhibit TORC2 in yeast and mammalian cells. Using fluorescent reporters of various lipids in budding yeast, we show that exposure to these small molecules causes mobilization of PM ergosterol as well as inhibition of TORC2. TORC2 inhibition results in activation of the PM-ER sterol transporters Lam2 and Lam4

SUBMITTER: Tettamanti MG 

PROVIDER: S-EPMC12705765 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature