RT Journal Article
T1 Ltc1 localization by EMC regulates cell membrane fluidity to facilitate membrane protein biogenesis
A1 Berraquero, Modesto
A1 Álvarez Tallada, Víctor
A1 Jiménez, Juan
K1 Biochemistry
K1 Cell biology
K1 Molecular biology
AB The EMC complex, a highly conserved transmembrane chaperone in the endoplasmic reticulum (ER), has been associated in humans with sterol homeostasis and a myriad of different cellular activities, rendering the mechanism of EMC functionality enigmatic. Using fission yeast, we demonstrate that the EMC complex facilitates the biogenesis of the sterol transfer protein Lam6/Ltc1 at ER-plasma membrane and ER-mitochondria contact sites. Cells that lose EMC function sequester unfolded Lam6/Ltc1 and other proteins at the mitochondrial matrix, leading to surplus ergosterol, cold-sensitive growth, and mitochondrial dysfunctions. Remarkably, inhibition of ergosterol biosynthesis, but also fluidization of cell membranes to counteract their rigidizing effects, reduce the ER-unfolded protein response and rescue growth and mitochondrial defects in EMC-deficient cells. These results suggest that EMC-assisted biogenesis of Lam6/Ltc1 may provide, through ergosterol homeostasis, optimal membrane fluidity to facilitate biogenesis of other ER-membrane proteins.
PB Elsevier Inc. Cell Press
YR 2025
FD 2025-03-21
LK https://hdl.handle.net/10433/26092
UL https://hdl.handle.net/10433/26092
LA en
NO iScience 28, 112096, 2025 ª 2025
NO Universidad Pablo de Olavide. Departamento de Biología Molecular e Ingeniería Bioquímica
DS RIO
RD May 22, 2026