Uniplex Assembly

Contributor: Saverio Marchi
{"name":"Uniplex 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Theorem

Information

The Uniporter complex (Uniplex) allows Ca2+ accumulation inside the mitochondrial matrix. It is composed by channel subunits (MCU, MCUb/CCDC109b and SMDT1/EMRE) and regulatory subunits (the MICU family and MCUR1). Structural studies report that MCU assembles as a tetramer, and EMRE is in a 1:1 stoichiometry with the MCU subunits. MICU1 forms heterodimers with MICU2 at the intermembrane space, regulating MCU opening/closure on the basis of cytosolic Ca2+ concentration.

 

References:

Kamer KJ, Mootha VK. The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol. 2015 Sep;16(9):545-53. doi: 10.1038/nrm4039. Epub 2015 Aug 19. PMID: 26285678.

Fan M, Zhang J, Tsai CW, Orlando BJ, Rodriguez M, Xu Y, Liao M, Tsai MF, Feng L. Structure and mechanism of the mitochondrial Ca2+ uniporter holocomplex. Nature. 2020 Jun;582(7810):129-133. doi: 10.1038/s41586-020-2309-6. Epub 2020 May 20. PMID: 32494073.

Wang Y, Nguyen NX, She J, Zeng W, Yang Y, Bai XC, Jiang Y. Structural Mechanism of EMRE-Dependent Gating of the Human Mitochondrial Calcium Uniporter. Cell. 2019 May 16;177(5):1252-1261.e13. doi: 10.1016/j.cell.2019.03.050. Epub 2019 May 9. PMID: 31080062.

Payne R, Hoff H, Roskowski A, Foskett JK. MICU2 Restricts Spatial Crosstalk between InsP3R and MCU Channels by Regulating Threshold and Gain of MICU1-Mediated Inhibition and Activation of MCU. Cell Rep. 2017 Dec 12;21(11):3141-3154. doi: 10.1016/j.celrep.2017.11.064. PMID: 29241542.

Wu W, Shen Q, Zhang R, Qiu Z, Wang Y, Zheng J, Jia Z. The structure of the MICU1-MICU2 complex unveils the regulation of the mitochondrial calcium uniporter. EMBO J. 2020 Oct 1;39(19):e104285. doi: 10.15252/embj.2019104285. Epub 2020 Aug 13. PMID: 32790952.

Petrungaro C, Zimmermann KM, Küttner V, Fischer M, Dengjel J, Bogeski I, Riemer J. The Ca(2+)-Dependent Release of the Mia40-Induced MICU1-MICU2 Dimer from MCU Regulates Mitochondrial Ca(2+) Uptake. Cell Metab. 2015 Oct 6;22(4):721-33. doi: 10.1016/j.cmet.2015.08.019. Epub 2015 Sep 17. PMID: 26387864.

 

Link to other Databases:

Reactome: https://reactome.org/content/detail/R-HSA-8953461

HumanCyc: https://humancyc.org/HUMAN/NEW-IMAGE?type=ENZYME&object=CPLX66-479

KEGG: https://www.genome.jp/dbget-bin/www_bget?pathway:map04020

Mitochondrial processes

Demonstrative and biological steps

Dynamic view

Mito-location

Not Available/Not Relevant
    M
    Matrix
      IM
      Inner Membrane
        IMS
        Inter-Membrane Space
          OM
          Outer Membrane
            PMS
            Peri-Mitochondrial Space

              Dynamic mito-location