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A conserved ER‐membrane complex facilitates phospholipid exchange between the ER and mitochondria (758.5)
Author(s) -
Lahiri Sujoy,
Chao Jesse,
Tavassoli Shabnam,
Wong Andrew,
Young Barry,
Loewen Christopher,
Prinz William
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.758.5
Subject(s) - mitochondrion , microbiology and biotechnology , endoplasmic reticulum , phosphatidylethanolamine , membrane contact site , organelle , inner mitochondrial membrane , biogenesis , biology , chemistry , phospholipid , biochemistry , membrane protein , integral membrane protein , membrane , phosphatidylcholine , gene
The objective of this study is to find the mechanism of lipid exchange between the endoplasmic reticulum (ER) and mitochondria. Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the ER to mitochondria. Transfer is thought to occur at regions of close contact of these organelles and to be nonvesicular, but the mechanism is not known. Here we used a novel genetic screen in S. cerevisiae to identify mutants with defects in lipid exchange between the ER and mitochondria. We show that a strain missing multiple components of the conserved ER‐membrane proteins complex (EMC) has decreased phosphatidylserine (PS) transport from the ER to mitochondria. Mitochondria from this strain have significantly reduced levels of PS and its derivative phosphatidylethanolamine (PE). Cells lacking EMC proteins and the ER‐mitochondria tethering complex called ERMES (the ER‐mitochondria encounter structure) are inviable, and PS transfer to mitochondria is dramatically reduced, suggesting that the EMC also functions as a tether. These defects are corrected by expression of an engineered ER‐mitochondrial tethering protein that artificially tethers the ER to mitochondria. EMC mutants have a significant reduction in the amount of ER associated with mitochondria, even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that the EMC interacts with the mitochondrial TOM complex protein, Tom5, and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth. Grant Funding Source : NIDDK intramural research program