RT Journal Article
A1 Ferreira, Joana Veríssimo
A1 Ahmed, Yara
A1 Heunis, Tiaan
A1 Jain, Aamna
A1 Johnson, Errin
A1 Räschle, Markus
A1 Ernst, Robert
A1 Vanni, Stefano
A1 Carvalho, Pedro
T1 Pex30-dependent membrane contact sites maintain ER lipid homeostasis
JF Journal of Cell Biology
JO J Cell Biol
YR 2025
DO 10.1083/jcb.202409039
OP e202409039
VO 224
IS 7
SN 0021-9525
AB In eukaryotic cells, communication between organelles and the coordination of their activities depend on membrane contact sites (MCS). How MCS are regulated under the dynamic cellular environment remains poorly understood. Here, we investigate how Pex30, a membrane protein localized to the endoplasmic reticulum (ER), regulates multiple MCS in budding yeast. We show that Pex30 is critical for the integrity of ER MCS with peroxisomes and vacuoles. This requires the dysferlin (DysF) domain on the Pex30 cytosolic tail. This domain binds to phosphatidic acid (PA) both in vitro and in silico, and it is important for normal PA metabolism in vivo. The DysF domain is evolutionarily conserved and may play a general role in PA homeostasis across eukaryotes. We further show that the ER–vacuole MCS requires a Pex30 C-terminal domain of unknown function and that its activity is controlled by phosphorylation in response to metabolic cues. These findings provide new insights into the dynamic nature of MCS and their coordination with cellular metabolism.
RD 5/24/2025
UL https://doi.org/10.1083/jcb.202409039