Home LiteratureArticle Details
PMID: 22992592 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Endoplasmic reticulum-mitochondria contacts: function of the junction.

Nature reviews. Molecular cell biology ·Vol. 13 ·No. 10 ·2012-10-00 ·Pages 607-25

Rowland AA, Voeltz GK

Abstract

The most well-characterized organelle contact sites are those between the endoplasmic reticulum (ER) and mitochondria. Increased understanding is being gained of how ER-mitochondria contact sites are organized and which factors converge at this interface, some of which may provide a tethering function. The role of the ER-mitochondria junction in coordinating the functions of these two organelles is also becoming clearer, and it has been shown to be involved in the regulation of lipid synthesis, Ca(2+) signalling and the control of mitochondrial biogenesis and intracellular trafficking.

MeSH Terms
Animals Calcium Signaling Endoplasmic Reticulum/metabolism,ultrastructure Lipids/biosynthesis Mitochondria/metabolism,ultrastructure Mitochondrial Membranes/metabolism,ultrastructure Mitochondrial Turnover Protein Transport Signal Transduction
Chemicals
Lipids
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Rowland Ashley A
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, 80309, USA.
Voeltz Gia K
References (84)
84 references, click to expand
  1. Dnm1 forms spirals that are structurally tailored to fit mitochondria.
    J Cell Biol. 2005 Sep 26;170(7):1021-7 PMID: 16186251
  2. Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase.
    Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20728-33 PMID: 19098100
  3. An ER-mitochondria tethering complex revealed by a synthetic biology screen.
    Science. 2009 Jul 24;325(5939):477-81 PMID: 19556461
  4. Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane.
    C R Biol. 2005 Jul;328(7):616-31 PMID: 15992745
  5. Mitofusin 2 tethers endoplasmic reticulum to mitochondria.
    Nature. 2008 Dec 4;456(7222):605-10 PMID: 19052620
  6. The mitochondrial calcium uniporter is a highly selective ion channel.
    Nature. 2004 Jan 22;427(6972):360-4 PMID: 14737170
  7. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization.
    Dev Cell. 2008 Feb;14(2):193-204 PMID: 18267088
  8. Multiple pathways influence mitochondrial inheritance in budding yeast.
    Genetics. 2008 Feb;178(2):825-37 PMID: 18245340
  9. Gem1 and ERMES do not directly affect phosphatidylserine transport from ER to mitochondria or mitochondrial inheritance.
    Traffic. 2012 Jun;13(6):880-90 PMID: 22409400
  10. Endoplasmic reticulum dynamics, inheritance, and cytoskeletal interactions in budding yeast.
    Mol Biol Cell. 2002 Mar;13(3):854-65 PMID: 11907267
  11. Composition and topology of the endoplasmic reticulum-mitochondria encounter structure.
    J Mol Biol. 2011 Nov 4;413(4):743-50 PMID: 21945531
  12. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p.
    J Cell Biol. 2000 Oct 16;151(2):367-80 PMID: 11038183
  13. Interorganelle transport of aminoglycerophospholipids.
    Biochim Biophys Acta. 2000 Jun 26;1486(1):97-107 PMID: 10856716
  14. Mitochondrial movement and morphology depend on an intact actin cytoskeleton in Aspergillus nidulans.
    Cell Motil Cytoskeleton. 2000 Jan;45(1):42-50 PMID: 10618165
  15. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis.
    Dev Cell. 2001 Oct;1(4):515-25 PMID: 11703942
  16. MAM: more than just a housekeeper.
    Trends Cell Biol. 2009 Feb;19(2):81-8 PMID: 19144519
  17. Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction.
    EMBO J. 2011 Feb 2;30(3):556-68 PMID: 21183955
  18. Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum.
    Nat Cell Biol. 2007 Oct;9(10):1160-6 PMID: 17828249
  19. Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast.
    Curr Biol. 2011 Dec 6;21(23):1994-9 PMID: 22119524
  20. Aux1p/Swa2p is required for cortical endoplasmic reticulum inheritance in Saccharomyces cerevisiae.
    Mol Biol Cell. 2001 Sep;12(9):2614-28 PMID: 11553703
  21. Phospholipid synthesis in a membrane fraction associated with mitochondria.
    J Biol Chem. 1990 May 5;265(13):7248-56 PMID: 2332429
  22. Hereditary spastic paraplegias: membrane traffic and the motor pathway.
    Nat Rev Neurosci. 2011 Jan;12(1):31-42 PMID: 21139634
  23. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis.
    Mol Biol Cell. 2004 Nov;15(11):5001-11 PMID: 15356267
  24. The WD repeat protein, Mdv1p, functions as a molecular adaptor by interacting with Dnm1p and Fis1p during mitochondrial fission.
    J Cell Biol. 2002 Aug 5;158(3):445-52 PMID: 12163467
  25. The myosin-related motor protein Myo2 is an essential mediator of bud-directed mitochondrial movement in yeast.
    J Cell Biol. 2011 Aug 8;194(3):473-88 PMID: 21807878
  26. Dynamics and inheritance of the endoplasmic reticulum.
    J Cell Sci. 2004 Jun 15;117(Pt 14):2871-8 PMID: 15197242
  27. The role of PML in the control of apoptotic cell fate: a new key player at ER-mitochondria sites.
    Cell Death Differ. 2011 Sep;18(9):1450-6 PMID: 21475307
  28. Membrane lipids: where they are and how they behave.
    Nat Rev Mol Cell Biol. 2008 Feb;9(2):112-24 PMID: 18216768
  29. Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission.
    Mol Biol Cell. 2003 May;14(5):1953-63 PMID: 12802067
  30. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.
    J Cell Biol. 2003 Jan 20;160(2):189-200 PMID: 12527753
  31. Progressive sheet-to-tubule transformation is a general mechanism for endoplasmic reticulum partitioning in dividing mammalian cells.
    Mol Biol Cell. 2012 Jul;23(13):2424-32 PMID: 22573885
  32. The endoplasmic reticulum: a multifunctional signaling organelle.
    Cell Calcium. 2002 Nov-Dec;32(5-6):235-49 PMID: 12543086
  33. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division.
    J Cell Biol. 2000 Oct 16;151(2):353-66 PMID: 11038182
  34. Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization.
    Cell. 2010 Sep 17;142(6):889-901 PMID: 20850011
  35. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter.
    Nature. 2011 Jun 19;476(7360):336-40 PMID: 21685888
  36. Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface.
    Mol Cell. 2010 Jul 9;39(1):121-32 PMID: 20603080
  37. Pushing for answers: is myosin V directly involved in moving mitochondria?
    J Cell Biol. 2008 Apr 7;181(1):15-8 PMID: 18391069
  38. RALA and RALBP1 regulate mitochondrial fission at mitosis.
    Nat Cell Biol. 2011 Aug 07;13(9):1108-15 PMID: 21822277
  39. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells.
    Mol Biol Cell. 2001 Aug;12(8):2245-56 PMID: 11514614
  40. The ER in 3D: a multifunctional dynamic membrane network.
    Trends Cell Biol. 2011 Dec;21(12):709-17 PMID: 21900009
  41. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release.
    Science. 2010 Nov 26;330(6008):1247-51 PMID: 21030605
  42. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.
    Science. 1998 Jun 12;280(5370):1763-6 PMID: 9624056
  43. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent.
    J Cell Biol. 2006 May 22;173(4):545-57 PMID: 16717129
  44. Actin-dependent mitochondrial motility in mitotic yeast and cell-free systems: identification of a motor activity on the mitochondrial surface.
    J Cell Biol. 1995 Jul;130(2):345-54 PMID: 7615636
  45. Cisternal organization of the endoplasmic reticulum during mitosis.
    Mol Biol Cell. 2009 Aug;20(15):3471-80 PMID: 19494040
  46. Making heads or tails of phospholipids in mitochondria.
    J Cell Biol. 2011 Jan 10;192(1):7-16 PMID: 21220505
  47. A conserved membrane-binding domain targets proteins to organelle contact sites.
    J Cell Sci. 2012 Jan 1;125(Pt 1):49-58 PMID: 22250200
  48. Temperature-sensitive yeast mutants defective in mitochondrial inheritance.
    J Cell Biol. 1990 Sep;111(3):967-76 PMID: 2202739
  49. ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules.
    J Cell Biol. 2010 Aug 9;190(3):363-75 PMID: 20696706
  50. Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor.
    Science. 1996 Jul 26;273(5274):503-7 PMID: 8662540
  51. Staying in touch: the molecular era of organelle contact sites.
    Trends Biochem Sci. 2011 Nov;36(11):616-23 PMID: 21958688
  52. The morphology proteins Mdm12/Mmm1 function in the major beta-barrel assembly pathway of mitochondria.
    EMBO J. 2007 May 2;26(9):2229-39 PMID: 17410204
  53. Complex formation with Ypt11p, a rab-type small GTPase, is essential to facilitate the function of Myo2p, a class V myosin, in mitochondrial distribution in Saccharomyces cerevisiae.
    Mol Cell Biol. 2002 Nov;22(22):7744-57 PMID: 12391144
  54. Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells.
    J Cell Biol. 2010 Dec 13;191(6):1141-58 PMID: 21149567
  55. Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells.
    J Cell Sci. 2009 Jun 15;122(Pt 12):1979-89 PMID: 19454478
  56. Endoplasmic reticulum remains continuous and undergoes sheet-to-tubule transformation during cell division in mammalian cells.
    J Cell Biol. 2007 Dec 3;179(5):895-909 PMID: 18056408
  57. Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.
    J Cell Biol. 1994 Sep;126(6):1361-73 PMID: 8089171
  58. Mitochondria as sensors and regulators of calcium signalling.
    Nat Rev Mol Cell Biol. 2012 Sep;13(9):566-78 PMID: 22850819
  59. Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway.
    J Cell Biol. 2004 Oct 11;167(1):87-98 PMID: 15479738
  60. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast.
    Nat Cell Biol. 1999 Sep;1(5):298-304 PMID: 10559943
  61. T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis.
    Mol Cell Biol. 1997 Jun;17(6):3005-12 PMID: 9154798
  62. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice.
    Nat Cell Biol. 2009 Aug;11(8):958-66 PMID: 19578372
  63. Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons.
    Mol Biol Cell. 2006 Apr;17(4):2057-68 PMID: 16467387
  64. Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels.
    J Cell Biol. 2006 Dec 18;175(6):901-11 PMID: 17178908
  65. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria.
    Science. 1993 Oct 29;262(5134):744-7 PMID: 8235595
  66. Mitochondria: in sickness and in health.
    Cell. 2012 Mar 16;148(6):1145-59 PMID: 22424226
  67. Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death.
    J Cell Biol. 2007 May 7;177(3):439-50 PMID: 17470634
  68. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells.
    Mol Biol Cell. 2008 Jun;19(6):2402-12 PMID: 18353969
  69. The class V myosin motor protein, Myo2, plays a major role in mitochondrial motility in Saccharomyces cerevisiae.
    J Cell Biol. 2008 Apr 7;181(1):119-30 PMID: 18391073
  70. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis.
    Science. 2003 Apr 4;300(5616):135-9 PMID: 12624178
  71. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.
    J Biol Chem. 2007 Apr 13;282(15):11521-9 PMID: 17301055
  72. Homology of SMP domains to the TULIP superfamily of lipid-binding proteins provides a structural basis for lipid exchange between ER and mitochondria.
    Bioinformatics. 2010 Aug 15;26(16):1927-31 PMID: 20554689
  73. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter.
    Nature. 2011 Jun 19;476(7360):341-5 PMID: 21685886
  74. ER tubules mark sites of mitochondrial division.
    Science. 2011 Oct 21;334(6054):358-62 PMID: 21885730
  75. Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae.
    J Cell Biol. 2003 Dec 22;163(6):1255-66 PMID: 14691136
  76. Mmr1p is a mitochondrial factor for Myo2p-dependent inheritance of mitochondria in the budding yeast.
    EMBO J. 2004 Jul 7;23(13):2520-30 PMID: 15201867
  77. Structural and functional features and significance of the physical linkage between ER and mitochondria.
    J Cell Biol. 2006 Sep 25;174(7):915-21 PMID: 16982799
  78. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane.
    Mol Cell. 1999 Nov;4(5):815-26 PMID: 10619028
  79. Is Alzheimer's disease a disorder of mitochondria-associated membranes?
    J Alzheimers Dis. 2010;20 Suppl 2:S281-92 PMID: 20421691
  80. A 3D analysis of yeast ER structure reveals how ER domains are organized by membrane curvature.
    J Cell Biol. 2011 Apr 18;193(2):333-46 PMID: 21502358
  81. The conserved GTPase Gem1 regulates endoplasmic reticulum-mitochondria connections.
    Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14151-6 PMID: 21825164
  82. Ca2+ hot spots on the mitochondrial surface are generated by Ca2+ mobilization from stores, but not by activation of store-operated Ca2+ channels.
    Mol Cell. 2010 Apr 23;38(2):280-90 PMID: 20417605
  83. Myosin-dependent endoplasmic reticulum motility and F-actin organization in plant cells.
    Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6894-9 PMID: 20351265
  84. Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes.
    J Biol Chem. 2000 Nov 3;275(44):34534-40 PMID: 10938271
Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm3440
Published
2012-10-00
Epub
2012-00-20
Pages
607-25
Language
English
Region
England
NLM ID
100962782
PMCID
PMC5111635
Subset
IM
Grants
NIGMS NIH HHS · R01 GM083977 · United States
NIGMS NIH HHS · T32 GM007135 · United States
NIGMS NIH HHS · GM07135 · United States
NIGMS NIH HHS · R01GM083977 · United States
External Links
PubMed source DOI: 10.1038/nrm3440 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2