TABLE 1.
Summary of membrane contact sites (MCSs).
| Contact site | Date Of Discovery | Organism | Proposed function | Used Tools for MCSs | Identified tethers |
| ER-PM | 1957 (Porter and Palade, 1957) | Mammalian | lipid transfer; activation of store-operated Ca2+ entry; autophagosome biogenesis | EM, ET, Confocal, FM, TIRFM | E-Syts (Schauder et al., 2014), GRAMD2a (Besprozvannaya et al., 2018), VAP-B-Nir2 (Kim et al., 2015), VAP-ORPs (Jansen et al., 2011), JPs (Takeshima et al., 2000; Landstrom et al., 2007), STIM1-Orail-hTRPC1 (Liou et al., 2007; Jardin et al., 2008) |
| Yeast | membrane complex formation and localization | EM, FM, Confocal, FRET | Scs2-Scs22 (Manford et al., 2012), Tcb1/2/3 (Manford et al., 2012), Osh2/3 (Levine and Munro, 2001), Ist2 (Manford et al., 2012) | ||
| ER-Mitochondria | 1959 (Copeland and Dalton, 1959) | Mammalian | Ca2+ exchange; lipid exchange; scission of mitochondria; autophagosome biogenesis | EM, FM, Confocal, PLA, FRET, SR-FACT | IP3R-GRP75-VDAC (Rizzuto et al., 1993; Szabadkai et al., 2006; D’Eletto et al., 2018), GRP75-TG2 (D’Eletto et al., 2018), BAP31-FIS1 (Iwasawa et al., 2011), Mfn2-Mfn2/Mfn1-Mfn2 (Naon et al., 2016), VAP-PTPIP51 (De Vos et al., 2012), Lam6 (Elbaz-Alon et al., 2015) |
| Yeast (ERMES) |
lipid exchange; phospholipid synthesis and cell growth; sterols transport | EM, FM, Confocal, SIM, TIRFM | ERMES complex (Kornmann et al., 2009; Kawano et al., 2018), Gem1 (Kornmann et al., 2011), Mmmr1 (Swayne et al., 2011), TOM5 (Lahiri et al., 2014), Lam6 (Elbaz-Alon et al., 2015), Ltc1-TOM70/71 (Murley et al., 2015), Num1 (Lackner et al., 2013) | ||
| ER-Endosome |
2009 (Rocha et al., 2009) | Mammalian | sterol sensing and endosome positioning; cholesterol transfer; endosomal tubule fission regulation | EM, FM, Confocal, 3D-SIM, PLA, FRET | VAP-A-STARD3/STARD3NL (Alpy et al., 2013), VAP-A-ORP1L (Rocha et al., 2009), ORP5-NPC1 (Du et al., 2011), Protrudin (Raiborg et al., 2015), PTP1B-EGFR (Eden et al., 2010), Rab5 (Hsu et al., 2018), Spastin-IST1 (Allison et al., 2017), VAP-OSBP-PI4P (Dong et al., 2016), TMCC1-Coronin1C (Hoyer et al., 2018), PTP1B-G-CSFR (Palande et al., 2011) |
| ER-Golgi | 1988 (Schweizer et al., 1988) | Mammalian | lipid exchange | EM, FM, Cryo-EM, Confocal, FRET | VAP-PI4P-OSBP (Mesmin et al., 2013; Jamecna et al., 2019), VAP-CERT (Hanada et al., 2003), VAP-FAPP2 (D’Angelo et al., 2007), VAP-Nir2 (Litvak et al., 2005) |
| Yeast | ceramides transfer | EM, FM, APEX2 | Nvj2 (Liu et al., 2017) | ||
| ER-LD | 2006 (Robenek et al., 2006) | Mammalian | LD growth regulation | Confocal, SIM, APEX | Rab18-NRZ (NAG-RINT1-ZW10) (Xu et al., 2018) |
| C. elegans | LD expansion | EM, Confocal | FATP1-DGAT2 (Xu et al., 2012) | ||
| Drosophila | LD growth regulation | EM, ET, Confocal, LLSM | Seipin (Wang et al., 2016) | ||
| ER-Peroxisome | 1987 (Yamamoto and Fahimi, 1987) | Mammalian | peroxisome growth; lipid homeostasis | SIM | VAPs-ACBD4 (Costello et al., 2017), VAPs-ACBD5 (Hua et al., 2017) |
| Yeast | peroxisome growth | Confocal | Pex3-Inp1-Pex3 (Knoblach et al., 2013), Pex30 (Joshi et al., 2018) | ||
| ER-Lysosome | 2018 (Atakpa et al., 2018) | Mammalian | Ca2+ exchange | TIRFM, STORM, LLSM, FIB-SEM | unknown |
| ER-Autophagosome | 2016 (Wijdeven et al., 2016) | Mammalian | lipid transfer | Cryo-EM, Confocal, FRET | LTP-ATG2, VAP-A-ORP1L (Wijdeven et al., 2016) |
| ER-Vacuole | 2000 (Pan et al., 2000) | Yeast | selectively sterols transport | FM, BiFC | Ltc1-Vac8 (Murley et al., 2015; Kakimoto et al., 2018), Nvj3-Mdm1 (Henne et al., 2015) |
| ER-DB | 2020 (Dong et al., 2020) | Mammalian | unknown | SR-FACT | unknown |
| Mitochondria-Golgi | 2007 (Ouasti et al., 2007) | Mammalian | apoptosis related | TEM, FM | Fas (CD95/Apo1) (Ouasti et al., 2007) |
| Mitochondria-Lysosome | 2002 (Ponka et al., 2002) | Mammalian | unknown | EM, Confocal, SIM, FRET, SR-FACT | unknown |
| Mitochondria-Endosome | 2002 (Ponka et al., 2002) | Mammalian | early endosomal-mitochondrial contacts and transferrin uptake regulation | EM, FM, SR-FACT | Rab5 (Hsu et al., 2018) |
| Mitochondria-Peroxisome | 2007 (Schrader and Yoon, 2007) | Mammalian | unknown | LLSM, BiFC, Confocal, STEDM | unknown |
| Mitochondria-LD | 2011 (Wang et al., 2011) | Mammalian | contact regulation | EM, SR-FACT | Perilipin-5 (Wang et al., 2011) |
| Mitochondria-Vacuole (vCLAMP) |
2014 (Honscher et al., 2014) | Yeast | survival in starvation and stress | EM, BiFC | TOM40-Vps39, Mcp1-Vps13 (Gonzalez Montoro et al., 2018) (vCLAMP) |
| Mitochondria-DB | 2020 (Dong et al., 2020) | Mammalian | mitochondrial fission | SR-FACT | unknown |
| Golgi-Autophagosome | 2015 (Biazik et al., 2015) | Mammalian | autophagosome formation | EM, ET | unknown |
| Lysosome-Peroxisome | 2015 (Chu et al., 2015) | Mammalian | cholesterol transfer | FM, LLSM | Syt7 (Chu et al., 2015; Valm et al., 2017) |
| Lysosome-Autophagosome | 1992 (Lawrence and Brown, 1992) | Mammalian | autophagosome formation | EM, ET, FM | Rab7-HOPS related complex (Jiang et al., 2014) |
| Yeast | autophagosome formation | EM, ET, FM | Ypt7-HOPS related complex (Kirisako et al., 1999) | ||
| Lysosome-Endosome | 1999 (Ohashi et al., 1999) | Mammalian | proper lysosomal digestive functions | EM, FM | Vamp8-Syntaxin 7 (Mullock et al., 2000), |
| Yeast | endosome fusion regulation | FM | Rab7-HOPS-Rab7 (Nordmann et al., 2010; Balderhaar and Ungermann, 2013) | ||
| Lysosome-LD | 2014 (Dugail, 2014) | Mammalian | lipid homeostasis | EM, FM, LLSM | PLIN2-HSC70-LAMP2A (Olzmann and Carvalho, 2019) |
| Lysosome-Golgi | 2018 (Hao et al., 2018) | Mammalian | amino acid supply response | FM, PLA | mTORC1-Rheb (Hao et al., 2018) |
| Peroxisome-LD | 2006 (Binns et al., 2006) | Mammalian | fatty acid trafficking | FIB-SEM, Confocal, LLSM, BiFC | M1 Spastin-ABCD1-ESCRT-III (Prinz et al., 2020) |
| Yeast | fatty acid trafficking | FIB-SEM, Confocal, LLSM, BiFC | M1 Spastin-ABCD1-ESCRT-III (Prinz et al., 2020) | ||
| Peroxisome-PM | 2018 (Kakimoto et al., 2018) | Yeast | unknown | BiFC | unknown |
| Peroxisome-Vacuole | 2018 (Kakimoto et al., 2018) | Yeast | unknown | BiFC | unknown |
| Nucleus-Vacuole | 1976 (Severs et al., 1976) | Yeast | microautophagy related | BiFC | Nvj1p-Vac8p (Kvam and Goldfarb, 2006), Lam6-Vac8 (Elbaz-Alon et al., 2015) |
| Nucleus-DB | 2020 (Dong et al., 2020) | Mammalian | nuclear membrane formation | SR-FACT | unknown |
| LD-PM | 2018 (Kakimoto et al., 2018) | Yeast | unknown | BiFC | unknown |
| LD-Vacuole | 2018 (Kakimoto et al., 2018) | Yeast | unknown | BiFC | unknown |
| Vacuole-PM | 2018 (Kakimoto et al., 2018) | Yeast | unknown | BiFC | unknown |
The table summarizes MCSs and related information in different organisms. PM, plasma membrane; LD, lipid droplet; DB, Dark-vacuole body; vCLAMP, vacuolar and mitochondrial patch; ERMES, ER-mitochondria encounter structure; EM, electron microscopy; TEM, transmission electron microscope; Cryo-EM, cryogenic electron microscopy; ET, electron tomography; FIB-SEM, focused ion beam-scanning EM; FM, fluorescence microscope; Confocal, confocal microscopy; SIM, structured illumination microscopy; 3D-SIM, three-dimensional structured illumination microscopy; TIRFM, total internal reflection fluorescence microscopy; SR-FACT, super-resolution fluorescence-assisted diffraction computational tomography; LLSM, lattice light-sheet microscopy; STORM, stochastic optical reconstruction microscopy; STEDM, stimulated emission depletion microscopy; PLA, proximity ligation assay; FRET, fluorescence resonance energy transfer; BiFC, bimolecular fluorescence complementation; APEX, engineered peroxidase; APEX2, engineered variant of soybean ascorbate peroxidase.