A Conserved Endoplasmic Reticulum Membrane Protein Complex (EMC) Facilitates Phospholipid Transfer from the ER to Mitochondria
Open accessAbstract
Mitochondrial membrane biogenesis and lipid metabolism require phospholipid transfer from the endoplasmic reticulum (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 protein complex (EMC) has decreased phosphatidylserine (PS) transfer 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, 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 tethered to mitochondria even though ERMES remained intact in these mutants, suggesting that the EMC performs an additional tethering function to ERMES. We find that all Emc proteins interact with the mitochondrial translocase of the outer membrane (TOM) complex protein Tom5 and this interaction is important for PS transfer and cell growth, suggesting that the EMC forms a tether by associating with the TOM complex. Together, our findings support that the EMC tethers ER to mitochondria, which is required for phospholipid synthesis and cell growth.
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- Authors
- Lahiri, S., Chao, J. T., Tavassoli, S., Wong, A. K. O., Choudhary, V., Young, B. P., Loewen, C. J. R., & Prinz, W. A.
- Affiliations
- National Institutes of Health (US)
- University of British Columbia (CA)
- Corresponding author
- Loewen, Christopher J. R.
- Prinz, William A.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-14
- Volume
- 12
- Issue
- 10
- Pages
- e1001969
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC4196738
- OpenAlex
- W2035944529
- Cited by
- 306
- References
- 55
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 24 · 2023: 16 · 2022: 20 · 2021: 27 · 2020: 35 · 2019: 29 · 2018: 36 · 2017: 31 · 2016: 34 · 2015: 31 · 2014: 3
- FWCI
- 13.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Tula Foundation
- Michael Smith Health Research BC
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- electromagnetic compatibility, phospholipid transfer, ER-mitochondria tethering, ERMES, phosphatidylserine, phosphatidylethanolamine, TOM complex, lipid exchange, Saccharomyces cerevisiae
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Endoplasmic Reticulum, Mitochondria, Phosphatidylserines, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Mitochondrial Membrane Transport Proteins, Genome-Wide Association Study
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