A Phospholipid Transfer Function of ER-Mitochondria Encounter Structure Revealed in Vitro
Open accessAbstract
As phospholipids are synthesized mainly in the endoplasmic reticulum (ER) and mitochondrial inner membranes, how cells properly distribute specific phospholipids to diverse cellular membranes is a crucial problem for maintenance of organelle-specific phospholipid compositions. Although the ER-mitochondria encounter structure (ERMES) was proposed to facilitate phospholipid transfer between the ER and mitochondria, such a role of ERMES is still controversial and awaits experimental demonstration. Here we developed a novel in vitro assay system with isolated yeast membrane fractions to monitor phospholipid exchange between the ER and mitochondria. With this system, we found that phospholipid transport between the ER and mitochondria relies on membrane intactness, but not energy sources such as ATP, GTP or the membrane potential across the mitochondrial inner membrane. We further found that lack of the ERMES component impairs the phosphatidylserine transport from the ER to mitochondria, but not the phosphatidylethanolamine transport from mitochondria to the ER. This in vitro assay system thus offers a powerful tool to analyze the non-vesicular phospholipid transport between the ER and mitochondria.
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Mdm12, Mdm34, and Mmm1 have synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domains, and the ERMES complex mediates lipid transport.
“Mdm12, Mdm34, and Mmm1 have synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domains [24], and the ERMES complex mediates lipid transport [25,26].”
From In Candida glabrata, ERMES Component GEM1 Controls Mitochondrial Morphology, mtROS, and Drug Efflux Pump Expression, Resulting in Azole Susceptibility (2023) · cites this paper as [26]
The Discussion reports that ERMES components are involved in phosphatidylserine transport from the ER to mitochondria, supporting a role in lipid transport. It also says that whether the ERMES complex directly mediates lipid transfer remains unclear; the cited claim states that stronger conclusion without qualification. The SMP-domain clause is attached to a different citation. (LLM, conf=0.88)
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Structure–Function Insights into Direct Lipid Transfer between Membranes by Mmm1–Mdm12 of ERMES
Kawano, S., Tamura, Y., Kojima, R., Bala, S., Asai, E., Michel, A. H., Kornmann, B., Riezman, I., Riezman, H., Sakae, Y., et al. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201704119 · Cited by 148 · see citing works
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“Mdm12, Mdm34, and Mmm1 have synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domains [24], and the ERMES complex mediates lipid transport [25,26].”
Background
- Authors
- Kojima, R., Endo, T., & Tamura, Y.
- Affiliations
- Yamagata University (JP)
- Kyoto Sangyo University (JP)
- Corresponding author
- Endo, Toshiya
- Tamura, Yasushi
- Venue
- Scientific Reports
- Published
- 2016-07-29
- Volume
- 6
- Issue
- 1
- Pages
- 30777-30777
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4965753
- OpenAlex
- W2490403655
- Cited by
- 91
- References
- 46
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 12 · 2019: 14 · 2018: 4 · 2017: 17 · 2016: 3
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15K14507, 14J00404, 22227003, CREST, 15H05595, 15H05705)
- Core Research for Evolutional Science and Technology
- 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
- ERMES, phospholipid transfer, endoplasmic reticulum, mitochondria, phosphatidylserine transport, membrane integrity, in vitro assay
- MeSH terms
- Biological Transport, Endoplasmic Reticulum, Mitochondria, Phosphatidylethanolamines, Phosphatidylserines, Phospholipids, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Mitochondrial Membranes, In Vitro Techniques
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