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Updated: Sep 20, 2025

Three-dimensional Characterization of Interorganelle Contact Sites in Hepatocytes using Serial Section Electron Microscopy
Published on: June 9, 2022
Pex30-dependent membrane contact sites maintain ER lipid homeostasis
Joana Veríssimo Ferreira1, Yara Ahmed2, Tiaan Heunis1
1Sir William Dunn School of Pathology, University of Oxford , Oxford, UK.
None:
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.
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