TABLE 1.
List of MERCS-Regulating Proteins.
| Gene Name | Localization | How to assess the roles in MERCS formation | Interactors | Other Roles | Evolutionary conservation | References |
| ATAD3A | Mitochondria (IMM, OMM) | - | Steroidogenesis, Cholesterol homeostasis, Cristae structure maintenance | Baudier, 2018; Issop et al., 2015 | ||
| BAP31 | ER | Fis1 | Proapoptotic | Iwasawa et al., 2011 | ||
| CISD2 | Mitochondria (OMM), ER | TEM, Immunofluorescence, Ca2+ transfer (in WFS2-patient-derived cells) (Rouzier et al., 2017) | GIMAP5 | Wolfram syndrome type 2 (WFS2)-related gene | Wang et al., 2014; Rouzier et al., 2017 | |
| CKAP4 | ER | TEM, Split-GFP, Ca2+ transfer | VDAC2 | Harada et al., 2020 | ||
| Drp1 | Cytoplasm, Mitochondria (OMM) | Immunofluorescence, Ca2+ transfer (in Mul1-deficient cells) (Prudent et al., 2015) | Mitochondrial fission | Prudent et al., 2015 | ||
| EMC | ER | TEM (in yeast) | SLC25A46? | Transmembrane helix insertase | Conserved from yeast | Lahiri et al., 2014 |
| EMD (Emerin) | Nucleus, ER | FATE1 | Causal gene of Emery–Dreifuss muscular dystrophy | Doghman-Bouguerra et al., 2016 | ||
| FATE1 | Mitochondria (OMM), Mitochondria-associated membrane (MAM) | TEM, Immunofluorescence, Ca2+ transfer | EMD/Emerin? | Antiapoptotic | Doghman-Bouguerra et al., 2016 | |
| Fis1 | Mitochondria (OMM) | BAP31 | Mitochondrial fission, Proapoptotic | Iwasawa et al., 2011 | ||
| FKBP8 | Mitochondria (OMM), ER | TEM, Ca2+ transfer | Unknown | Antiapoptotic, Mitophagy | Kwak et al., 2020 | |
| FUNDC1 | Mitochondria (OMM) | TEM (Wu et al., 2017) | IP3R2, Calnexin (under hypoxia) | Mitophagy, Mitochondrial fission, Ca2+ regulation |
Wu et al., 2016; Wu et al., 2017 |
|
| GIMAP5 | MAM, ER? | CISD2 | Wang et al., 2014 | |||
| Gp78 (AMFR) | ER | TEM, Immunofluorescence | Mfn1/2 (ubiquitination) | E3 ubiquitin ligase, ER-associated protein degradation | Wang et al., 2015 | |
| GRP75 | Cytoplasm (MAM) | Ca2+ transfer | IP3R, VDAC1 | Szabadkai et al., 2006 | ||
| INF2 | ER | Immunofluorescence | Spire1C | Actin polymerization | Manor et al., 2015 | |
| IP3R | ER | TEM (Bartok et al., 2019) | Grp75 | Ca2+ transport | Szabadkai et al., 2006; Bartok et al., 2019 | |
| Mfn1 | Mitochondria (OMM) | Mfn2 | Mitochondrial fusion | De Brito and Scorrano, 2008 | ||
| Mfn2 | Mitochondria (OMM), ER | Ca2+ transfer (De Brito and Scorrano, 2008) TEM (Cosson et al., 2012; Filadi et al., 2015; Naon et al., 2016) | Mfn2, Mfn1 | Mitochondrial fusion | De Brito and Scorrano, 2008; Cosson et al., 2012; Filadi et al., 2018 | |
| Miga2 | Mitochondria (OMM) | TEM (in fly) (Xu et al., 2020) | VAPA, VAPB | Mitochondrial fusion | Freyre et al., 2019; Xu et al., 2020 | |
| MITOL (MARCH5) | MAM, Mitochondria | Immunofluorescence, In vitro ER-mitochondria binding assay, Ca2+ transfer (Sugiura et al., 2013) SBF-SEM (Nagashima et al., 2019) | Mfn2 (ubiquitination) | E3 ubiquitin ligase | Sugiura et al., 2013; Nagashima et al., 2019 | |
| Mul1 (MAPL) | Mitochondria | Immunofluorescence, Ca2 + transfer (Prudent et al., 2015) TEM, Immunofluorescence in stimulated emission depletion microscopy (STED) (Puri et al., 2019) | Mfn2 (ubiquitination), Drp1 (SUMOlylation) | E3 ubiquitin ligase | Prudent et al., 2015; Puri et al., 2019 | |
| PDZD8 | ER (partially MAM) | Serial SEM, Ca2+ transfer, | Unknown | Resident in ER-late endosome/lysosome contacts | Potential Ortholog (Paralog) of MMM1 | Hirabayashi et al., 2017 |
| PS2 | ER | Immunofluorescence, Ca2+ transfer | Mfn2 | Causally linked to familial Alzheimer’s disease (FAD) | Filadi et al., 2016 | |
| Reep1 | ER, Mitochondria | Split-RLuc8 assay (in Reep1-overexpressing cells) | Unknown | Hereditary spastic paraplegias (HSPs)-associated gene | Lim et al., 2015 | |
| RHOT1/2 (MIRO1/2) | Mitochondria (OMM) | TEM, Immunofluorescence, Ca2+ transfer (Modi et al., 2019) | IP3R? | Mitochondrial motility (Microtubule binding) | GEM1 in yeast | Kornmann et al., 2011; S. Lee et al., 2016; Modi et al., 2019; |
| RMDN3 (PTPIP51) | Mitochondria (OMM) | Ca2+ transfer (De vos et al., 2012) TEM, Immunofluorescence (Stoica et al., 2014) | VAPB | De vos et al., 2012; Stoica et al., 2014; Gomez-Suaga et al., 2017; Fecher et al., 2019 | ||
| RRBP1 | ER | TEM (Anastasia et al., 2021) | SYNJ2BP | Kinesin binding | Hung et al., 2017; Anastasia et al., 2021 | |
| SLC25A46 | Mitochondria (OMM) | EMC component? | Phospholipid exchange | Janer et al., 2016 | ||
| Spire1C | Mitochondria (OMM) | Immunofluorescence | INF2 | Actin nucleation | Manor et al., 2015 | |
| SYNJ2BP | Mitochondria (OMM) | TEM (in SYNJ2BP-overexpressing cells) | RRBP1 | Negative regulator of angiogenesis, tumor growth and metastasis | Hung et al., 2017 | |
| Tom70 | Mitochondria (OMM) | SPLICS, Immunofluorescence, Ca2+ transfer | IP3R3 | Translocase of OMM | Filadi et al., 2018 | |
| VAPB | ER | Ca2+ transfer (De vos et al., 2012) TEM, Immunofluorescence (Stoica et al., 2014) | RMDN3 | Resident in ER–endosome contacts, ER–golgi contacts and ER–PM contacts | De vos et al., 2012; Stoica et al., 2014; Freyre et al., 2019; Xu et al., 2020 | |
| VDAC1 | Mitochondria (OMM) | TEM (Bosc et al., 2020) | GRP75 | Ca2+ transport | Szabadkai et al., 2006; Bosc et al., 2020 | |
| VDAC2 | Mitochondria (OMM) | CKAP4 | Ca2+ transport | Harada et al., 2020 | ||
| VPS13A | MAM | TEM (Muñoz-Braceras et al., 2019) Immunofluorescence (Kumar et al., 2018) SPLICS (Yeshaw et al., 2019) | VAPA, VAPB | Autophagy regulation, Lipid droplet motility | Kumar et al., 2018; Muñoz-Braceras et al., 2019; Yeshaw et al., 2019. | |
| TMX1 | ER, MAM (palmitoylated) | TEM, Ca2+ transfer | Unknown | Raturi et al., 2016 | ||
| TG2 | Cytoplasm (MAM) | TEM, Proximity ligation assay, Immunofluorescence | GRP75 | Posttranslational modification | D‘Eletto et al., 2018 |
ATAD3A, ATPase family AAA domain-containing protein 3A; BAP31, B-cell receptor-associated protein 31; CISD2, CDGSH iron-sulfur domain-containing protein 2; CKAP4, cytoskeleton-associated protein 4; Drp1, dynamin-related protein 1; EMC, endoplasmic reticulum membrane protein complex; ER, endoplasmic reticulum; FATE1, fetal and adult testis-expressed transcript protein; Fis1, fission protein 1; FKBP8, FK506-binding protein 8; FUNDC1, FUN14 domain-containing protein 1; GIMAP5, GTPase immunity-associated protein family member 5; GRP75, glucose-regulated protein 75; IMM, inner mitochondrial membrane; INF2, Inverted formin 2; IP3R, inositol 1,4,5-trisphosphate receptor; MAM, mitochondria-associated membrane; MERCS, mitochondria–endoplasmic reticulum contact site; Mfn2, mitofusin 2; Miga2, mitoguardin 2; MITOL, Mitochondrial ubiquitin ligase; Mul1, mitochondrial ubiquitin protein ligase 1; Mul1, mitochondrial E3 ubiquitin protein ligase 1; OMM, outer membrane of mitochondria; PDZD8, PDZ domain-containing protein 8; PM, plasma membrane; PS2, presenilin 2; Reep1, receptor expression-enhancing protein 1; RHOT1, Ras homolog family member T1; RMDN3, regulator of microtubule dynamics protein 3; RRBP1, ribosome-binding protein 1; SLC25A46, solute carrier family 25 member 46; SPLICS, split GFP-based contact site sensors; SYNJ2BP, synaptojanin-2-binding protein; TEM, transmission electron microscopy; TG2, transglutaminase type 2; TMX1, thioredoxin-related transmembrane protein 1; TMX1, transmembrane protein 1; Tom7, translocase of outer membrane 7; VAPB, VAMP-associated protein B; VDAC, voltage-dependent anion channel; VPS13A, vacuolar protein sorting-associated protein 13 A.