Skip to main content

Advertisement

SpringerLink
Log in

A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Early eukaryotic cells emerged from the compartmentalization of metabolic processes into specific organelles through the development of an endomembrane system (ES), a precursor of the endoplasmic reticulum (ER), which was essential for their survival. Recently, substantial evidence emerged on how organelles communicate among themselves and with the plasma membrane (PM) through contact sites (CSs). From these studies, the ER—the largest single structure in eukaryotic cells—emerges as a central player communicating with all organelles to coordinate cell functions and respond to external stimuli to maintain cellular homeostasis. Herein we review the functional insights into the ER–CSs with other organelles in a physiological perspective. We hypothesize that, in addition to the primitive role by the ES in the appearance of proto-eukaryotes, its successor—the ER—emerges as the key coordinator of inter-organelle/PM communication. The ER thus appears to be the ‘maestro’ driving eukaryotic cell evolution by incorporating new functions/organelles, while remaining the real coordinator overarching cellular functions and orchestrating them with the external milieu.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

AD:

Alzheimer's disease

ALS:

Amyotrophic lateral sclerosis

AM:

Arbuscular mycorrhizae

CHL:

Chloroplast

EE(s):

Early endosome(s)

ER:

Endoplasmic reticulum

ERAD:

ER-associated (protein) degradation

ERGIC:

ER-Golgi intermediate compartment

ERMES:

ER-mitochondrial tethering complex

FTD:

Fronto-temporal dementia

MAM:

Mitochondria-associated ER membranes

ES:

Endomembrane system

GFP:

Green fluorescent protein

IM:

Isolation membrane

LD(s):

Lipid droplet(s)

LE(s):

Late endosome(s)

LTP(s):

Lipid-transfer protein(s)

MCS(s):

Membrane contact site(s)

MITO:

Mitochondria

MT (s):

Microtubule(s)

PD:

Parkinson’s disease

PH:

Pleckstrin homology (domain)

PLAM(s):

Plastid-associated membranes

PLD:

Plasmodesmata

PM:

Plasma membrane

PMCS(s):

Plasma membrane contact site(s)

PMP(s):

Peroxisomal membrane proteins(s)

PPA:

Pre-penetration apparatus

PV(s):

Parasitophorous vacuole(s)

PBs:

Processing bodies

RER:

Rough ER

SER:

Smooth ER

SE(s):

Steryl ester(s)

SOCE:

Store-operated Ca2+ entry

STIM:

Stromal interaction molecule

TEM:

Transmission electron microscopy

TG:

Triacylglycerol

TPC(s):

Two-pore channel(s)

TRP(s):

Transient receptor potential channel(s)

VAP(s):

Vesicle-associated membrane protein-associated protein(s

References

  1. Field MC, Sali A, Rout MP (2011) On a bender—BARs, ESCRTs, COPs, and finally getting your coat. J Cell Biol 193(6):963–972. https://doi.org/10.1083/jcb.201102042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jékely G (2007) Origin of eukaryotic endomembranes: a critical evaluation of different model scenarios. In: Eukaryotic membranes and cytoskeleton: origins and evolution. Springer, New York, pp 38–51. https://doi.org/10.1007/978-0-387-74021-8_3

  3. de Duve C (2007) The origin of eukaryotes: a reappraisal. Nat Rev Genet 8(5):395–403. https://doi.org/10.1038/nrg2071

    Article  CAS  PubMed  Google Scholar 

  4. Cavalier-Smith T (2014) The neomuran revolution and phagotrophic origin of eukaryotes and cilia in the light of intracellular coevolution and a revised tree of life. Cold Spring Harb Perspect Biol 6(9):a016006. https://doi.org/10.1101/cshperspect.a016006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mast FD, Barlow LD, Rachubinski RA, Dacks JB (2014) Evolutionary mechanisms for establishing eukaryotic cellular complexity. Trends Cell Biol 24(7):435–442. https://doi.org/10.1016/j.tcb.2014.02.003

    Article  CAS  PubMed  Google Scholar 

  6. Baum DA (2015) A comparison of autogenous theories for the origin of eukaryotic cells. Am J Bot 102(12):1954–1965. https://doi.org/10.3732/ajb.1500196

    Article  CAS  PubMed  Google Scholar 

  7. Martin WF, Garg S, Zimorski V (2015) Endosymbiotic theories for eukaryote origin. Philos Trans R Soc B Biol Sci. https://doi.org/10.1098/rstb.2014.0330

    Article  Google Scholar 

  8. Gould SB, Garg SG, Martin WF (2016) Bacterial vesicle secretion and the evolutionary origin of the eukaryotic endomembrane system. Trends Microbiol 24(7):525–534. https://doi.org/10.1016/j.tim.2016.03.005

    Article  CAS  PubMed  Google Scholar 

  9. Dacks JB, Field MC (2018) Evolutionary origins and specialisation of membrane transport. Curr Opin Cell Biol 53:70–76. https://doi.org/10.1016/j.ceb.2018.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Blackstone C, Prinz WA (2016) Keeping in shape. Elife 5:e20468. https://doi.org/10.7554/eLife.20468

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shibata Y, Voeltz GK, Rapoport TA (2006) Rough sheets and smooth tubules. Cell 126(3):435–439. https://doi.org/10.1016/j.cell.2006.07.019

    Article  CAS  PubMed  Google Scholar 

  12. Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA (2006) A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124(3):573–586. https://doi.org/10.1016/j.cell.2005.11.047

    Article  CAS  PubMed  Google Scholar 

  13. Borgese N, Francolini M, Snapp E (2006) Endoplasmic reticulum architecture: structures in flux. Curr Opin Cell Biol 18(4):358–364. https://doi.org/10.1016/j.ceb.2006.06.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Westrate LM, Lee JE, Prinz WA, Voeltz GK (2015) Form follows function: the importance of endoplasmic reticulum shape. Annu Rev Biochem 84:791–811. https://doi.org/10.1146/annurev-biochem-072711-163501

    Article  CAS  PubMed  Google Scholar 

  15. Ravindran MS, Bagchi P, Cunningham CN, Tsai B (2016) Opportunistic intruders: how viruses orchestrate ER functions to infect cells. Nat Rev Microbiol 14(7):407–420. https://doi.org/10.1038/nrmicro.2016.60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Raffaello A, Mammucari C, Gherardi G, Rizzuto R (2016) Calcium at the center of cell signaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci 41(12):1035–1049. https://doi.org/10.1016/j.tibs.2016.09.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jacquemyn J, Cascalho A, Goodchild RE (2017) The ins and outs of endoplasmic reticulum-controlled lipid biosynthesis. EMBO Rep 18(11):1905–1921. https://doi.org/10.15252/embr.201643426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Koch GL (1990) The endoplasmic reticulum and calcium storage. BioEssays 12(11):527–531. https://doi.org/10.1002/bies.950121105

    Article  CAS  PubMed  Google Scholar 

  19. Vance JE (2014) MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochem Biophys Acta 1841(4):595–609. https://doi.org/10.1016/j.bbalip.2013.11.014

    Article  CAS  PubMed  Google Scholar 

  20. English AR, Voeltz GK (2013) Endoplasmic reticulum structure and interconnections with other organelles. Cold Spring Harb Perspect Biol 5(4):a013227. https://doi.org/10.1101/cshperspect.a013227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Phillips MJ, Voeltz GK (2016) Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol 17(2):69–82. https://doi.org/10.1038/nrm.2015.8

    Article  CAS  PubMed  Google Scholar 

  22. Rowland AA, Voeltz GK (2012) Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 13(10):607–625. https://doi.org/10.1038/nrm3440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Raturi A (1833) Simmen T (2013) Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM). Biochem Biophys Acta 1:213–224. https://doi.org/10.1016/j.bbamcr.2012.04.013

    Article  CAS  Google Scholar 

  24. Marchi S, Patergnani S (1837) Pinton P (2014) The endoplasmic reticulum–mitochondria connection: one touch, multiple functions. Biochim Biophys Acta Bioenerg 4:461–469. https://doi.org/10.1016/j.bbabio.2013.10.015

    Article  CAS  Google Scholar 

  25. Scorrano L, De Matteis MA, Emr S, Giordano F, Hajnóczky G, Kornmann B, Lackner LL, Levine TP, Pellegrini L, Reinisch K, Rizzuto R, Simmen T, Stenmark H, Ungermann C, Schuldiner M (2019) Coming together to define membrane contact sites. Nat Commun 10(1):1287. https://doi.org/10.1038/s41467-019-09253-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cohen S, Valm AM, Lippincott-Schwartz J (2018) Interacting organelles. Curr Opin Cell Biol 53:84–91. https://doi.org/10.1016/j.ceb.2018.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eisenberg-Bord M, Shai N, Schuldiner M, Bohnert M (2016) A tether is a tether is a tether: tethering at membrane contact sites. Dev Cell 39(4):395–409. https://doi.org/10.1016/j.devcel.2016.10.022

    Article  CAS  PubMed  Google Scholar 

  28. Spang A (2018) The endoplasmic reticulum-the caring mother of the cell. Curr Opin Cell Biol 53:92–96. https://doi.org/10.1016/j.ceb.2018.06.004

    Article  CAS  PubMed  Google Scholar 

  29. Wu H, Carvalho P, Voeltz GK (2018) Here, there, and everywhere: The importance of ER membrane contact sites. Science. https://doi.org/10.1126/science.aan5835

    Article  PubMed  PubMed Central  Google Scholar 

  30. Erpapazoglou Z, Mouton-Liger F, Corti O (2017) From dysfunctional endoplasmic reticulum-mitochondria coupling to neurodegeneration. Neurochem Int 109:171–183. https://doi.org/10.1016/j.neuint.2017.03.021

    Article  CAS  PubMed  Google Scholar 

  31. Joshi AS, Zhang H, Prinz WA (2017) Organelle biogenesis in the endoplasmic reticulum. Nat Cell Biol 19(8):876–882. https://doi.org/10.1038/ncb3579

    Article  CAS  PubMed  Google Scholar 

  32. Smith JJ, Aitchison JD (2013) Peroxisomes take shape. Nat Rev Mol Cell Biol 14(12):803–817. https://doi.org/10.1038/nrm3700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim P (2017) Peroxisome biogenesis: a union between two organelles. Curr Biol 27(7):R271–R274. https://doi.org/10.1016/j.cub.2017.02.052

    Article  CAS  PubMed  Google Scholar 

  34. van Vliet AR, Verfaillie T, Agostinis P (1843) (2014) New functions of mitochondria associated membranes in cellular signaling. Biochim Biophys Acta Mol Cell Res 10:2253–2262. https://doi.org/10.1016/j.bbamcr.2014.03.009

    Article  CAS  Google Scholar 

  35. Csordás G, Renken C, Várnai P, Walter L, Weaver D, Buttle KF, Balla T, Mannella CA, Hajnóczky G (2006) Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 174(7):915–921. https://doi.org/10.1083/jcb.200604016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK (2011) ER tubules mark sites of mitochondrial division. Science 334(6054):358–362. https://doi.org/10.1126/science.1207385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, Voeltz GK (2010) ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules. J Cell Biol 190(3):363–375. https://doi.org/10.1083/jcb.200911024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Martinvalet D (2018) The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses. Cell Death Dis 9(3):336. https://doi.org/10.1038/s41419-017-0237-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gr S, Bianchi K, Pt V, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Ts B, Rizzuto R (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 175(6):901–911. https://doi.org/10.1083/jcb.200608073

    Article  CAS  Google Scholar 

  40. Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T (2013) Autophagosomes form at ER–mitochondria contact sites. Nature 495(7441):389–393. https://doi.org/10.1038/nature11910

    Article  CAS  PubMed  Google Scholar 

  41. Area-Gomez E, de Groof AJC, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA (2009) Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am J Pathol 175(5):1810–1816. https://doi.org/10.2353/ajpath.2009.090219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tubbs E, Theurey P, Vial G, Bendridi N, Bravard A, Chauvin MA, Ji-Cao J, Zoulim F, Bartosch B, Ovize M, Vidal H, Rieusset J (2014) Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance. Diabetes 63(10):3279–3294. https://doi.org/10.2337/db13-1751

    Article  CAS  PubMed  Google Scholar 

  43. Lynes EM, Raturi A, Shenkman M, Sandoval CO, Yap MC, Wu J, Janowicz A, Myhill N, Benson MD, Campbell RE, Berthiaume LG, Lederkremer GZ, Simmen T (2013) Palmitoylation is the switch that assigns calnexin to quality control or ER Ca%3csup%3e2+%3c/sup%3e signaling. J Cell Sci 126(17):3893–3903. https://doi.org/10.1242/jcs.125856

    Article  CAS  PubMed  Google Scholar 

  44. Simmen T, Aslan JE, Blagoveshchenskaya AD, Thomas L, Wan L, Xiang Y, Feliciangeli SF, Hung CH, Crump CM, Thomas G (2005) PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis. EMBO J 24(4):717–729. https://doi.org/10.1038/sj.emboj.7600559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Arruda AP, Pers BM, Parlakgul G, Guney E, Inouye K, Hotamisligil GS (2014) Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nat Med 20(12):1427–1435. https://doi.org/10.1038/nm.3735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vance JE (1990) Phospholipid synthesis in a membrane fraction associated with mitochondria. J Biol Chem 265(13):7248–7256

    CAS  PubMed  Google Scholar 

  47. Stone SJ, Vance JE (2000) Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes. J Biol Chem 275(44):34534–34540. https://doi.org/10.1074/jbc.M002865200

    Article  CAS  PubMed  Google Scholar 

  48. Betz C, Stracka D, Prescianotto-Baschong C, Frieden M, Demaurex N, Hall MN (2013) mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci 110(31):12526–12534. https://doi.org/10.1073/pnas.1302455110

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tiemann K, Garri C, Lee SB, Malihi PD, Park M, Alvarez RM, Yap LP, Mallick P (2019) Loss of ER retention motif of AGR2 can impact mTORC signaling and promote cancer metastasis. Oncogene 38(16):3003–3018. https://doi.org/10.1038/s41388-018-0638-9

    Article  CAS  PubMed  Google Scholar 

  50. Sugiura A, Nagashima S, Tokuyama T, Amo T, Matsuki Y, Ishido S, Kudo Y, McBride Heidi M, Fukuda T, Matsushita N, Inatome R, Yanagi S (2013) MITOL regulates endoplasmic reticulum-mitochondria contacts via mitofusin2. Mol Cell 51(1):20–34. https://doi.org/10.1016/j.molcel.2013.04.023

    Article  CAS  PubMed  Google Scholar 

  51. Sebastian D, Hernandez-Alvarez MI, Segales J, Sorianello E, Munoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P, Oresic M, Pich S, Burcelin R, Palacin M, Zorzano A (2012) Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci USA 109(14):5523–5528. https://doi.org/10.1073/pnas.1108220109

    Article  PubMed  PubMed Central  Google Scholar 

  52. de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456(7222):605–610. https://doi.org/10.1038/nature07534

    Article  CAS  PubMed  Google Scholar 

  53. Gaigg B, Simbeni R, Hrastnik C, Paltauf F, Daum G (1995) Characterization of a microsomal subfraction associated with mitochondria of the yeast, Saccharomyces cerevisiae. Involvement in synthesis and import of phospholipids into mitochondria. Biochim Biophys Acta 1234(2):214–220

    Article  PubMed  Google Scholar 

  54. Achleitner G, Gaigg B, Krasser A, Kainersdorfer E, Kohlwein SD, Perktold A, Zellnig G, Daum G (1999) Association between the endoplasmic reticulum and mitochondria of yeast facilitates interorganelle transport of phospholipids through membrane contact. Eur J Biochem 264(2):545–553

    Article  CAS  PubMed  Google Scholar 

  55. Theurey P, Rieusset J (2017) Mitochondria-associated membranes response to nutrient availability and role in metabolic diseases. Trends Endocrinol Metab 28(1):32–45. https://doi.org/10.1016/j.tem.2016.09.002

    Article  CAS  PubMed  Google Scholar 

  56. Theurey P, Tubbs E, Vial G, Jacquemetton J, Bendridi N, Chauvin MA, Alam MR, Le Romancer M, Vidal H, Rieusset J (2016) Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver. J Mol Cell Biol 8(2):129–143. https://doi.org/10.1093/jmcb/mjw004

    Article  CAS  PubMed  Google Scholar 

  57. Loewen CJ, Roy A, Levine TP (2003) A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J 22(9):2025–2035. https://doi.org/10.1093/emboj/cdg201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Stoica R, De Vos KJ, Paillusson S, Mueller S, Sancho RM, Lau K-F, Vizcay-Barrena G, Lin W-L, Xu Y-F, Lewis J, Dickson DW, Petrucelli L, Mitchell JC, Shaw CE, Miller CCJ (2014) ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun 5:3996. https://doi.org/10.1038/ncomms4996

    Article  CAS  PubMed  Google Scholar 

  59. Ingerman E, Perkins EM, Marino M, Mears JA, McCaffery JM, Hinshaw JE, Nunnari J (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J Cell Biol 170(7):1021–1027. https://doi.org/10.1083/jcb.200506078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bleazard W, McCaffery JM, King EJ, Bale S, Mozdy A, Tieu Q, Nunnari J, Shaw JM (1999) The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1(5):298–304. https://doi.org/10.1038/13014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Labrousse AM, Zappaterra MD, Rube DA, van der Bliek AM (1999) C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol Cell 4(5):815–826

    Article  CAS  PubMed  Google Scholar 

  62. Smirnova E, Griparic L, Shurland DL, van der Bliek AM (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12(8):2245–2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shim S-H, Xia C, Zhong G, Babcock HP, Vaughan JC, Huang B, Wang X, Xu C, Bi G-Q, Zhuang X (2012) Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes. Proc Natl Acad Sci USA 109(35):13978–13983. https://doi.org/10.1073/pnas.1201882109

    Article  PubMed  PubMed Central  Google Scholar 

  64. Lewis SC, Uchiyama LF, Nunnari J (2016) ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science 353(6296):aaf5549. https://doi.org/10.1126/science.aaf5549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Krols M, van Isterdael G, Asselbergh B, Kremer A, Lippens S, Timmerman V, Janssens S (2016) Mitochondria-associated membranes as hubs for neurodegeneration. Acta Neuropathol 131(4):505–523. https://doi.org/10.1007/s00401-015-1528-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Burte F, Carelli V, Chinnery PF, Yu-Wai-Man P (2015) Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol 11(1):11–24. https://doi.org/10.1038/nrneurol.2014.228

    Article  CAS  PubMed  Google Scholar 

  67. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133. https://doi.org/10.1126/science.1134108

    Article  CAS  PubMed  Google Scholar 

  68. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148(6):1145–1159. https://doi.org/10.1016/j.cell.2012.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Blackstone C, O'Kane CJ, Reid E (2011) Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci 12(1):31–42. https://doi.org/10.1038/nrn2946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Schon EA, Area-Gomez E (2010) Is Alzheimer's disease a disorder of mitochondria-associated membranes? J Alzheimers Dis 20(Suppl 2):S281–292. https://doi.org/10.3233/jad-2010-100495

    Article  PubMed  Google Scholar 

  71. Hayashi T (2015) Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs. J Pharmacol Sci 127(1):2–5. https://doi.org/10.1016/j.jphs.2014.07.001

    Article  CAS  PubMed  Google Scholar 

  72. Thoudam T, Jeon J-H, Ha C-M, Lee I-K (2016) Role of mitochondria-associated endoplasmic reticulum membrane in inflammation-mediated metabolic diseases. Mediators Inflamm 2016:18. https://doi.org/10.1155/2016/1851420

    Article  CAS  Google Scholar 

  73. Baker RG, Hayden MS, Ghosh S (2011) NF-kappaB, inflammation, and metabolic disease. Cell Metab 13(1):11–22. https://doi.org/10.1016/j.cmet.2010.12.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329):221–225. https://doi.org/10.1038/nature09663

    Article  CAS  PubMed  Google Scholar 

  75. Bassoy EY, Kasahara A, Chiusolo V, Jacquemin G, Boydell E, Zamorano S, Riccadonna C, Pellegatta S, Hulo N, Dutoit V, Derouazi M, Dietrich PY, Walker PR, Martinvalet D (2017) ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells. EMBO J 36(11):1493–1512. https://doi.org/10.15252/embj.201695429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Giorgi C, Ito K, Lin HK, Santangelo C, Wieckowski MR, Lebiedzinska M, Bononi A, Bonora M, Duszynski J, Bernardi R, Rizzuto R, Tacchetti C, Pinton P, Pandolfi PP (2010) PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330(6008):1247–1251. https://doi.org/10.1126/science.1189157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wiley SE, Andreyev AY, Divakaruni AS, Karisch R, Perkins G, Wall EA, van der Geer P, Chen YF, Tsai TF, Simon MI, Neel BG, Dixon JE, Murphy AN (2013) Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis. EMBO Mol Med 5(6):904–918. https://doi.org/10.1002/emmm.201201429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Sano R, Annunziata I, Patterson A, Moshiach S, Gomero E, Opferman J, Forte M, d'Azzo A (2009) GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca(2+)-dependent mitochondrial apoptosis. Mol Cell 36(3):500–511. https://doi.org/10.1016/j.molcel.2009.10.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Lopez-Crisosto C, Pennanen C, Vasquez-Trincado C, Morales PE, Bravo-Sagua R, Quest AFG, Chiong M, Lavandero S (2017) Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology. Nat Rev Cardiol 14(6):342–360. https://doi.org/10.1038/nrcardio.2017.23

    Article  CAS  PubMed  Google Scholar 

  80. Prasad M, Kaur J, Pawlak KJ, Bose M, Whittal RM, Bose HS (2015) Mitochondria-associated endoplasmic reticulum membrane (MAM) regulates steroidogenic activity via steroidogenic acute regulatory protein (StAR)-voltage-dependent anion channel 2 (VDAC2) interaction. J Biol Chem 290(5):2604–2616. https://doi.org/10.1074/jbc.M114.605808

    Article  CAS  PubMed  Google Scholar 

  81. Zorzano A, Liesa M, Palacin M (2009) Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes. Int J Biochem Cell Biol 41(10):1846–1854. https://doi.org/10.1016/j.biocel.2009.02.004

    Article  CAS  PubMed  Google Scholar 

  82. Hernandez-Alvarez MI, Sebastian D, Vives S, Ivanova S, Bartoccioni P, Kakimoto P, Plana N, Veiga SR, Hernandez V, Vasconcelos N, Peddinti G, Adrover A, Jove M, Pamplona R, Gordaliza-Alaguero I, Calvo E, Cabre N, Castro R, Kuzmanic A, Boutant M, Sala D, Hyotylainen T, Oresic M, Fort J, Errasti-Murugarren E, Rodrigues CMP, Orozco M, Joven J, Canto C, Palacin M, Fernandez-Veledo S, Vendrell J, Zorzano A (2019) Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease. Cell 177(4):881–895.e817. https://doi.org/10.1016/j.cell.2019.04.010

    Article  CAS  PubMed  Google Scholar 

  83. Cooper GM (2000) Bioenergetics and metabolism—mitochondria, chloroplasts, and peroxisomes. In: The cell: a molecular approach, 2nd edn. Sinauer Associates, Sunderland

    Google Scholar 

  84. Schrader M, Grille S, Fahimi HD, Islinger M (2013) Peroxisome interactions and cross-talk with other subcellular compartments in animal cells. Subcell Biochem 69:1–22. https://doi.org/10.1007/978-94-007-6889-5_1

    Article  CAS  PubMed  Google Scholar 

  85. Sugiura A, Mattie S, Prudent J, McBride HM (2017) Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes. Nature 542(7640):251–254. https://doi.org/10.1038/nature21375

    Article  CAS  PubMed  Google Scholar 

  86. Hua R, Cheng D, Coyaud É, Freeman S, Di Pietro E, Wang Y, Vissa A, Yip CM, Fairn GD, Braverman N, Brumell JH, Trimble WS, Raught B, Kim PK (2017) VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis. J Cell Biol 216(2):367–377. https://doi.org/10.1083/jcb.201608128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Costello JL, Castro IG, Hacker C, Schrader TA, Metz J, Zeuschner D, Azadi AS, Godinho LF, Costina V, Findeisen P, Manner A, Islinger M, Schrader M (2017) ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER. J Cell Biol 216(2):331–342. https://doi.org/10.1083/jcb.201607055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schrader M, Godinho LF, Costello JL, Islinger M (2015) The different facets of organelle interplay-an overview of organelle interactions. Front Cell Dev Biol 3:56–56. https://doi.org/10.3389/fcell.2015.00056

    Article  PubMed  PubMed Central  Google Scholar 

  89. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141(4):668–681. https://doi.org/10.1016/j.cell.2010.04.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Odendall C, Dixit E, Stavru F, Bierne H, Franz KM, Durbin AF, Boulant S, Gehrke L, Cossart P, Kagan JC (2014) Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nat Immunol 15(8):717–726. https://doi.org/10.1038/ni.2915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Horner SM, Liu HM, Park HS, Briley J, Gale M Jr (2011) Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci USA 108(35):14590–14595. https://doi.org/10.1073/pnas.1110133108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Horner SM, Wilkins C, Badil S, Iskarpatyoti J, Gale M (2015) Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking. PLoS ONE 10(3):e0117963. https://doi.org/10.1371/journal.pone.0117963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. McNally KE, Cullen PJ (2018) Endosomal retrieval of cargo: retromer is not alone. Trends Cell Biol 28(10):807–822. https://doi.org/10.1016/j.tcb.2018.06.005

    Article  CAS  PubMed  Google Scholar 

  94. Friedman JR, Dibenedetto JR, West M, Rowland AA, Voeltz GK (2013) Endoplasmic reticulum-endosome contact increases as endosomes traffic and mature. Mol Biol Cell 24(7):1030–1040. https://doi.org/10.1091/mbc.E12-10-0733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zajac AL, Goldman YE, Holzbaur EL, Ostap EM (2013) Local cytoskeletal and organelle interactions impact molecular-motor- driven early endosomal trafficking. Curr Biol 23(13):1173–1180. https://doi.org/10.1016/j.cub.2013.05.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Phillips MJ, Voeltz GK (2015) Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol 17:69. https://doi.org/10.1038/nrm.2015.8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lelouvier B, Puertollano R (2011) Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway. J Biol Chem 286(11):9826–9832. https://doi.org/10.1074/jbc.M110.169185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Abe K, Puertollano R (2011) Role of TRP channels in the regulation of the endosomal pathway. Physiology (Bethesda) 26(1):14–22. https://doi.org/10.1152/physiol.00048.2010

    Article  CAS  Google Scholar 

  99. Ruas M, Rietdorf K, Arredouani A, Davis LC, Lloyd-Evans E, Koegel H, Funnell TM, Morgan AJ, Ward JA, Watanabe K, Cheng X, Churchill GC, Zhu MX, Platt FM, Wessel GM, Parrington J, Galione A (2010) Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking. Curr Biol 20(8):703–709. https://doi.org/10.1016/j.cub.2010.02.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Dong R, Saheki Y, Swarup S, Lucast L, Harper JW, De Camilli P (2016) Endosome-ER contacts control actin nucleation and retromer function through VAP-dependent regulation of PI4P. Cell 166(2):408–423. https://doi.org/10.1016/j.cell.2016.06.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Raiborg C, Wenzel EM, Pedersen NM, Olsvik H, Schink KO, Schultz SW, Vietri M, Nisi V, Bucci C, Brech A, Johansen T, Stenmark H (2015) Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth. Nature 520(7546):234–238. https://doi.org/10.1038/nature14359

    Article  CAS  PubMed  Google Scholar 

  102. Guillen-Samander A, Bian X, De Camilli P (2019) PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes. Proc Natl Acad Sci USA 116(45):22619–22623. https://doi.org/10.1073/pnas.1913509116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hoyer MJ, Chitwood PJ, Ebmeier CC, Striepen JF, Qi RZ, Old WM, Voeltz GK (2018) A novel class of ER membrane proteins regulates ER-associated endosome fission. Cell 175(1):254–265.e214. https://doi.org/10.1016/j.cell.2018.08.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Allison R, Edgar JR (2017) Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia. J Cell Biol 216(5):1337–1355. https://doi.org/10.1083/jcb.201609033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M (2003) Molecular machinery for non-vesicular trafficking of ceramide. Nature 426(6968):803–809. https://doi.org/10.1038/nature02188

    Article  CAS  PubMed  Google Scholar 

  106. D'Angelo G, Polishchuk E, Di Tullio G, Santoro M, Di Campli A, Godi A, West G, Bielawski J, Chuang CC, van der Spoel AC, Platt FM, Hannun YA, Polishchuk R, Mattjus P, De Matteis MA (2007) Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature 449(7158):62–67. https://doi.org/10.1038/nature06097

    Article  CAS  PubMed  Google Scholar 

  107. Litvak V, Dahan N, Ramachandran S, Sabanay H, Lev S (2005) Maintenance of the diacylglycerol level in the golgi apparatus by the Nir2 protein is critical for golgi secretory function. Nat Cell Biol 7(3):225–234. https://doi.org/10.1038/ncb1221

    Article  CAS  PubMed  Google Scholar 

  108. Mesmin B, Bigay J, Moser von Filseck J, Lacas-Gervais S, Drin G, Antonny B (2013) A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell 155(4):830–843. https://doi.org/10.1016/j.cell.2013.09.056

    Article  CAS  PubMed  Google Scholar 

  109. Perry RJ, Ridgway ND (2006) Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein. Mol Biol Cell 17(6):2604–2616. https://doi.org/10.1091/mbc.e06-01-0060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lev S (2010) Non-vesicular lipid transport by lipid-transfer proteins and beyond. Nat Rev Mol Cell Biol 11(10):739–750. https://doi.org/10.1038/nrm2971

    Article  CAS  PubMed  Google Scholar 

  111. Lev S, Ben Halevy D, Peretti D, Dahan N (2008) The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol 18(6):282–290. https://doi.org/10.1016/j.tcb.2008.03.006

    Article  CAS  PubMed  Google Scholar 

  112. Zamponi N, Zamponi E, Mayol GF, Lanfredi-Rangel A, Svard SG, Touz MC (2017) Endoplasmic reticulum is the sorting core facility in the Golgi-lacking protozoan Giardia lamblia. Traffic 18(9):604–621. https://doi.org/10.1111/tra.12501

    Article  CAS  PubMed  Google Scholar 

  113. Porter KR, Palade GE (1957) Studies on the endoplasmic reticulum. III. Its form and distribution in striated muscle cells. J Biophys Biochem Cytol 3(2):269–300. https://doi.org/10.1083/jcb.3.2.269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Carrasco S, Meyer T (2011) STIM proteins and the endoplasmic reticulum-plasma membrane junctions. Annu Rev Biochem 80:973–1000. https://doi.org/10.1146/annurev-biochem-061609-165311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Franzini-Armstrong C (2018) The relationship between form and function throughout the history of excitation-contraction coupling. J Gen Physiol 150(2):189–210. https://doi.org/10.1085/jgp.201711889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lunz V, Romanin C, Frischauf I (2019) STIM1 activation of Orai1. Cell Calcium 77:29–38. https://doi.org/10.1016/j.ceca.2018.11.009

    Article  CAS  PubMed  Google Scholar 

  117. Saheki Y, Camilli PD (2017) Endoplasmic reticulum-plasma membrane contact sites. Annu Rev Biochem 86(1):659–684. https://doi.org/10.1146/annurev-biochem-061516-044932

    Article  CAS  PubMed  Google Scholar 

  118. Chen YJ, Quintanilla CG, Liou J (2019) Recent insights into mammalian ER-PM junctions. Curr Opin Cell Biol 57:99–105. https://doi.org/10.1016/j.ceb.2018.12.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Orci L, Ravazzola M, Le Coadic M, Shen WW, Demaurex N, Cosson P (2009) From the Cover: STIM1-induced precortical and cortical subdomains of the endoplasmic reticulum. Proc Natl Acad Sci USA 106(46):19358–19362. https://doi.org/10.1073/pnas.0911280106

    Article  PubMed  PubMed Central  Google Scholar 

  120. Fernandez-Busnadiego R, Saheki Y, De Camilli P (2015) Three-dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites. Proc Natl Acad Sci USA 112(16):E2004–2013. https://doi.org/10.1073/pnas.1503191112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Franzini-Armstrong C, Jorgensen AO (1994) Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol 56:509–534. https://doi.org/10.1146/annurev.ph.56.030194.002453

    Article  CAS  PubMed  Google Scholar 

  122. Hogan PG, Rao A (2015) Store-operated calcium entry: mechanisms and modulation. Biochem Biophys Res Commun 460(1):40–49. https://doi.org/10.1016/j.bbrc.2015.02.110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Prakriya M, Lewis RS (2015) Store-operated calcium channels. Physiol Rev 95(4):1383–1436. https://doi.org/10.1152/physrev.00020.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Giordano F, Saheki Y, Idevall-Hagren O, Colombo SF, Pirruccello M, Milosevic I, Gracheva EO, Bagriantsev SN, Borgese N, De Camilli P (2013) PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell 153(7):1494–1509. https://doi.org/10.1016/j.cell.2013.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Saheki Y, Bian X, Schauder CM, Sawaki Y, Surma MA, Klose C, Pincet F, Reinisch KM, De Camilli P (2016) Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nat Cell Biol 18(5):504–515. https://doi.org/10.1038/ncb3339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Lees JA, Messa M, Sun EW, Wheeler H, Torta F, Wenk MR, De Camilli P, Reinisch KM (2017) Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion. Science 355(6326):eaah6171. https://doi.org/10.1126/science.aah6171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, De Camilli P (2015) PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER–plasma membrane contacts. Science 349(6246):428–432. https://doi.org/10.1126/science.aab1370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Sohn M, Korzeniowski M (2018) PI(4,5)P2 controls plasma membrane PI4P and PS levels via ORP5/8 recruitment to ER-PM contact sites. J Cell Biol 217(5):1797–1813. https://doi.org/10.1083/jcb.201710095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Sandhu J, Li S, Fairall L, Pfisterer SG, Gurnett JE, Xiao X, Weston TA, Vashi D, Ferrari A, Orozco JL, Hartman CL, Strugatsky D, Lee SD, He C, Hong C, Jiang H, Bentolila LA, Gatta AT, Levine TP, Ferng A, Lee R, Ford DA, Young SG, Ikonen E, Schwabe JWR, Tontonoz P (2018) Aster proteins facilitate nonvesicular plasma membrane to ER cholesterol transport in mammalian cells. Cell 175(2):514–529.e520. https://doi.org/10.1016/j.cell.2018.08.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Naito T, Ercan B, Krshnan L, Triebl A, Koh DHZ, Wei F-Y, Tomizawa K, Torta FT, Wenk MR, Saheki Y (2019) Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex. Elife. https://doi.org/10.7554/eLife.51401

    Article  PubMed  PubMed Central  Google Scholar 

  131. Johnson B, Leek AN, Solé L, Maverick EE, Levine TP, Tamkun MM (2018) Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB. Proc Natl Acad Sci USA 115(31):E7331–E7340. https://doi.org/10.1073/pnas.1805757115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Kirmiz M, Vierra NC, Palacio S, Trimmer JS (2018) Identification of VAPA and VAPB as Kv2 channel-interacting proteins defining endoplasmic reticulum-plasma membrane junctions in mammalian brain neurons. J Neurosci 38(35):7562–7584. https://doi.org/10.1523/jneurosci.0893-18.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vierra NC, Kirmiz M, van der List D, Santana LF, Trimmer JS (2019) Kv2.1 mediates spatial and functional coupling of L-type calcium channels and ryanodine receptors in mammalian neurons. Elife. https://doi.org/10.7554/eLife.49953

    Article  PubMed  PubMed Central  Google Scholar 

  134. Nakatsu F, Baskin JM, Chung J, Tanner LB, Shui G, Lee SY, Pirruccello M, Hao M, Ingolia NT, Wenk MR, De Camilli P (2012) PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity. J Cell Biol 199(6):1003–1016. https://doi.org/10.1083/jcb.201206095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Korzeniowski MK, Popovic MA, Szentpetery Z, Varnai P, Stojilkovic SS, Balla T (2009) Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides. J Biol Chem 284(31):21027–21035. https://doi.org/10.1074/jbc.M109.012252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Lacruz RS, Feske S (2015) Diseases caused by mutations in ORAI1 and STIM1. Ann NY Acad Sci 1356:45–79. https://doi.org/10.1111/nyas.12938

    Article  CAS  PubMed  Google Scholar 

  137. Ng AQE, Ng AYE, Zhang D (2020) Plasma membrane furrows control plasticity of ER-PM contacts. Cell Rep 30(5):1434–1446.e1437. https://doi.org/10.1016/j.celrep.2019.12.098

    Article  CAS  PubMed  Google Scholar 

  138. Zahumensky J, Malinsky J (2019) Role of MCC/eisosome in fungal lipid homeostasis. Biomolecules. https://doi.org/10.3390/biom9080305

    Article  PubMed  PubMed Central  Google Scholar 

  139. Barbosa AD, Siniossoglou S (1864) (2017) Function of lipid droplet-organelle interactions in lipid homeostasis. Biochim Biophys Acta Mol Cell Res 9:1459–1468. https://doi.org/10.1016/j.bbamcr.2017.04.001

    Article  CAS  Google Scholar 

  140. Schuldiner M, Bohnert M (1862) (2017) A different kind of love—lipid droplet contact sites. Biochim Biophys Acta Mol Cell Biol Lipids 10:1188–1196. https://doi.org/10.1016/j.bbalip.2017.06.005

    Article  CAS  Google Scholar 

  141. Wang H, Becuwe M, Housden BE, Chitraju C, Porras AJ, Graham MM, Liu XN, Thiam AR, Savage DB, Agarwal AK, Garg A, Olarte MJ, Lin Q, Frohlich F, Hannibal-Bach HK, Upadhyayula S, Perrimon N, Kirchhausen T, Ejsing CS, Walther TC, Farese RV (2016) Seipin is required for converting nascent to mature lipid droplets. Elife. https://doi.org/10.7554/eLife.16582

    Article  PubMed  PubMed Central  Google Scholar 

  142. Ugrankar R, Bowerman J, Hariri H, Chandra M, Chen K, Bossanyi M-F, Datta S, Rogers S, Eckert KM, Vale G, Victoria A, Fresquez J, McDonald JG, Jean S, Collins BM, Henne WM (2019) Drosophila Snazarus regulates a lipid droplet population at plasma membrane-droplet contacts in adipocytes. Dev Cell 50(5):557–572.e555. https://doi.org/10.1016/j.devcel.2019.07.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Datta S, Liu Y, Hariri H, Bowerman J, Henne WM (2019) Cerebellar ataxia disease–associated Snx14 promotes lipid droplet growth at ER–droplet contacts. J Cell Biol 218(4):1335–1351. https://doi.org/10.1083/jcb.201808133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Freyre CAC, Rauher PC, Ejsing CS, Klemm RW (2019) MIGA2 links mitochondria, the ER, and lipid droplets and promotes de novo lipogenesis in adipocytes. Mol Cell 76(5):811–825.e814. https://doi.org/10.1016/j.molcel.2019.09.011

    Article  CAS  PubMed  Google Scholar 

  145. Lamb CA, Yoshimori T, Tooze SA (2013) The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol 14(12):759–774. https://doi.org/10.1038/nrm3696

    Article  CAS  PubMed  Google Scholar 

  146. Wei Y, Liu M, Li X, Liu J, Li H (2018) Origin of the autophagosome membrane in mammals. Biomed Res Int 2018:1012789–1012789. https://doi.org/10.1155/2018/1012789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Wilkinson S (2020) Emerging principles of selective ER autophagy. J Mol Biol 432(1):185–205. https://doi.org/10.1016/j.jmb.2019.05.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Hübner CA, Dikic I (2020) ER-phagy and human diseases. Cell Death Differ 27(3):833–842. https://doi.org/10.1038/s41418-019-0444-0

    Article  PubMed  Google Scholar 

  149. Klionsky DJ, Cuervo AM, Dunn JWA, Levine B, van der Klei IJ, Seglen PO (2007) How shall i eat thee? Autophagy 3(5):413–416. https://doi.org/10.4161/auto.4377

    Article  PubMed  Google Scholar 

  150. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492. https://doi.org/10.1146/annurev.ph.28.030166.002251

    Article  PubMed  Google Scholar 

  151. Bae D, Moore KA, Mella JM (2019) Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress. J Cell Biol 218(4):1118–1127. https://doi.org/10.1083/jcb.201809027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Hurtley SM (2019) Lysosome repositioning. Science 363(6433):1297–1298. https://doi.org/10.1126/science.363.6433.1297-f

    Article  Google Scholar 

  153. Lim CY, Davis OB, Shin HR, Zhang J, Berdan CA, Jiang X, Counihan JL, Ory DS, Nomura DK (2019) ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann-Pick type C. Nat Cell Biol 21(10):1206–1218. https://doi.org/10.1038/s41556-019-0391-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Levin-Konigsberg R, Montano-Rendon F, Keren-Kaplan T, Li R, Ego B, Mylvaganam S, DiCiccio JE, Trimble WS (2019) Phagolysosome resolution requires contacts with the endoplasmic reticulum and phosphatidylinositol-4-phosphate signalling. Nat Cell Biol 21(10):1234–1247. https://doi.org/10.1038/s41556-019-0394-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Wong YC, Ysselstein D, Krainc D (2018) Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature 554(7692):382–386. https://doi.org/10.1038/nature25486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Banani SF, Rice AM, Peeples WB, Lin Y, Jain S, Parker R, Rosen MK (2016) Compositional control of phase-separated cellular bodies. Cell 166(3):651–663. https://doi.org/10.1016/j.cell.2016.06.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Boeynaems S, Alberti S, Fawzi NL, Mittag T, Polymenidou M, Rousseau F, Schymkowitz J, Shorter J, Wolozin B, Van Den Bosch L, Tompa P, Fuxreiter M (2018) Protein phase separation: a new phase in cell biology. Trends Cell Biol 28(6):420–435. https://doi.org/10.1016/j.tcb.2018.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Decker CJ, Parker R (2012) P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb Perspect Biol 4(9):a012286. https://doi.org/10.1101/cshperspect.a012286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Coller J, Parker R (2005) General translational repression by activators of mRNA decapping. Cell 122(6):875–886. https://doi.org/10.1016/j.cell.2005.07.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kilchert C, Weidner J, Prescianotto-Baschong C, Spang A (2010) Defects in the secretory pathway and high Ca2+ induce multiple P-bodies. Mol Biol Cell 21(15):2624–2638. https://doi.org/10.1091/mbc.E10-02-0099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Hubstenberger A, Courel M, Bénard M, Souquere S, Ernoult-Lange M, Chouaib R, Yi Z, Morlot J-B, Munier A, Fradet M, Daunesse M, Bertrand E, Pierron G, Mozziconacci J, Kress M, Weil D (2017) P-Body Purification reveals the condensation of repressed mRNA regulons. Mol Cell 68(1):144–157.e145. https://doi.org/10.1016/j.molcel.2017.09.003

    Article  CAS  PubMed  Google Scholar 

  162. Wang C, Schmich F, Srivatsa S, Weidner J, Beerenwinkel N, Spang A (2018) Context-dependent deposition and regulation of mRNAs in P-bodies. Elife 7:e29815. https://doi.org/10.7554/eLife.29815

    Article  PubMed  PubMed Central  Google Scholar 

  163. Khong A, Matheny T, Jain S, Mitchell SF, Wheeler JR, Parker R (2017) The stress granule transcriptome reveals principles of mRNA accumulation in stress granules. Mol Cell 68(4):808–820.e805. https://doi.org/10.1016/j.molcel.2017.10.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Markmiller S, Soltanieh S, Server KL, Mak R, Jin W, Fang MY, Luo EC, Krach F, Yang D, Sen A, Fulzele A, Wozniak JM, Gonzalez DJ, Kankel MW, Gao FB, Bennett EJ, Lecuyer E, Yeo GW (2018) Context-dependent and disease-specific diversity in protein interactions within stress granules. Cell 172(3):590–604.e513. https://doi.org/10.1016/j.cell.2017.12.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, Golan DE, Anderson P (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151(6):1257–1268. https://doi.org/10.1083/jcb.151.6.1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Lee JE, Cathey PI (2020) Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles. Science. https://doi.org/10.1126/science.aay7108

    Article  PubMed  PubMed Central  Google Scholar 

  167. Mehrshahi P, Stefano G, Andaloro JM, Brandizzi F, Froehlich JE, DellaPenna D (2013) Transorganellar complementation redefines the biochemical continuity of endoplasmic reticulum and chloroplasts. Proc Natl Acad Sci USA 110(29):12126–12131. https://doi.org/10.1073/pnas.1306331110

    Article  PubMed  PubMed Central  Google Scholar 

  168. Perez-Sancho J, Tilsner J, Samuels AL, Botella MA, Bayer EM, Rosado A (2016) Stitching organelles: organization and function of specialized membrane contact sites in plants. Trends Cell Biol 26(9):705–717. https://doi.org/10.1016/j.tcb.2016.05.007

    Article  CAS  PubMed  Google Scholar 

  169. Kaneko Y, Keegstra K (1996) Plastid biogenesis in embryonic pea leaf cells during early germination. Protoplasma 195(1):59–67. https://doi.org/10.1007/bf01279186

    Article  Google Scholar 

  170. Wooding FBP, Northcote DH (1965) Association of the endoplasmic reticulum and the plastids in acer and pinus. Am J Bot 52(5):526–531. https://doi.org/10.2307/2440270

    Article  Google Scholar 

  171. Hanson MR, Kohler RH (2001) GFP imaging: methodology and application to investigate cellular compartmentation in plants. J Exp Bot 52(356):529–539

    Article  CAS  PubMed  Google Scholar 

  172. Whatley JM, McLean B, Juniper BE (1991) Continuity of chloroplast and endoplasmic reticulum membranes in Phaseolus vulgaris. New Phytol 117(2):209–217. https://doi.org/10.1111/j.1469-8137.1991.tb04901.x

    Article  Google Scholar 

  173. Andersson MX, Goksor M, Sandelius AS (2007) Optical manipulation reveals strong attracting forces at membrane contact sites between endoplasmic reticulum and chloroplasts. J Biol Chem 282(2):1170–1174. https://doi.org/10.1074/jbc.M608124200

    Article  CAS  PubMed  Google Scholar 

  174. Griffing LR (2011) Laser stimulation of the chloroplast/endoplasmic reticulum nexus in tobacco transiently produces protein aggregates (boluses) within the endoplasmic reticulum and stimulates local ER remodeling. Mol Plant 4(5):886–895. https://doi.org/10.1093/mp/ssr072

    Article  CAS  PubMed  Google Scholar 

  175. Liebe S, Menzel D (1995) Actomyosin-based motility of endoplasmic reticulum and chloroplasts in Vallisneria mesophyll cells*. Biol Cell 85(2–3):207–222. https://doi.org/10.1016/0248-4900(96)85282-8

    Article  CAS  PubMed  Google Scholar 

  176. Schattat M, Barton K, Baudisch B, Klosgen RB, Mathur J (2011) Plastid stromule branching coincides with contiguous endoplasmic reticulum dynamics. Plant Physiol 155(4):1667–1677. https://doi.org/10.1104/pp.110.170480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Schattat M, Barton K, Mathur J (2011) Correlated behavior implicates stromules in increasing the interactive surface between plastids and ER tubules. Plant Signal Behav 6(5):715–718. https://doi.org/10.4161/psb.6.5.15085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Mehrshahi P, Johnny C, DellaPenna D (2014) Redefining the metabolic continuity of chloroplasts and ER. Trends Plant Sci 19(8):501–507. https://doi.org/10.1016/j.tplants.2014.02.013

    Article  CAS  PubMed  Google Scholar 

  179. Wang Z, Benning C (2012) Chloroplast lipid synthesis and lipid trafficking through ER-plastid membrane contact sites. Biochem Soc Trans 40(2):457–463. https://doi.org/10.1042/bst20110752

    Article  CAS  PubMed  Google Scholar 

  180. Block MA, Jouhet J (2015) Lipid trafficking at endoplasmic reticulum–chloroplast membrane contact sites. Curr Opin Cell Biol 35:21–29. https://doi.org/10.1016/j.ceb.2015.03.004

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

C. Almeida was the recipient of a fellowship from Fundação para a Ciência e Tecnologia, FCT, Portugal (fellowship SFRH/BPD/77720/2011). Work in MD Amaral’s lab is supported by UID/MULTI/04046/2019 centre grant (to BioISI) and research grants from FCT/MCTES Portugal (PTDC/BIM-MEC/2131/2014) “DiffTarget”, FCT/02/SAICT/2017/28800) “iDrugCF, “HIT-CF” and CF Trust UK (SRC 013).

Author information

Author notes

  1. Celso Almeida and Margarida D. Amaral have contributed equally to this article.

Authors and Affiliations

  1. Faculty of Sciences, BioISI, Biosystems and Integrative Sciences Institute, University of Lisboa, Campo Grande, C8 bdg, 1749-016, Lisbon, Portugal

    Celso Almeida & Margarida D. Amaral

Authors
  1. Celso Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margarida D. Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Celso Almeida or Margarida D. Amaral.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Almeida, C., Amaral, M.D. A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles. Cell. Mol. Life Sci. 77, 4729–4745 (2020). https://doi.org/10.1007/s00018-020-03523-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-020-03523-w

Keywords

Search

Navigation