Formation of MIB complex containing the MICOS complex causes curvature of mitochondrial inner membrane

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R-HSA-8949609
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Reaction [omitted]
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Homo sapiens
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Assembly of the MICOS complex on the inner mitochondrial membrane appears to cause curvature of the inner membrane into the matrix to form invaginations known as cristae (Guarani et al. 2015, Huynen et al. 2016). The order of steps by which the MICOS complex assembles is unknown, however the MICOS complex is known to contain two subcomplexes: the MIC60 subcomplex and the MIC10 subcomplex which may associate via CHCHD3 (MIC19, MINOS3) (Huynen et al. 2016, nomenclature of subunits in Pfanner et al. 2014). HSPA9 also associates with MIC10 (MINOS1) in the complex (Alkhaja et al. 2012). The oxidation state of MIC19 regulates assembly of the MICOS complex (Sakowska et al. 2015). QIL1 (MIC12, MIC13), which has a distant orthologue in yeast (Huynen et al. 2016), is required for assembly of MIC10, MIC26, and MIC27 into the MICOS complex but not for formation of the MIC60 subcomplex (Guarani et al. 2015, Anand et al. 2016, Zerbes et al. 2016). Mutations in QIL1 cause loss of MICOS complex assembly and cristae junction architecture (Guarani et al. 2016, Zeharia et al. 2016)
The MICOS complex associates with the SAM complex of the outer membrane to form the Mitochondrial Intermembrane space Bridging complex (MIB complex) that links the inner and outer membranes (Kozjak-Pavlovic et al. 2007, Xie et al. 2007, Ott et al. 2012, Ding et al. 2015, Huynen et al. 2016). Oligomerization of the MINOS1 (MIC10) subunit (Alkhaja et al. 2012) within the MIC10 subcomplex is responsible for the curvature of the inner membrane (inferred from yeast). Dimerization of the F1Fo ATP synthase occurs at the interior-most regions of the cristae to form the curvature there (inferred from yeast).

Literature References
PubMed ID Title Journal Year
17510655 Conserved roles of Sam50 and metaxins in VDAC biogenesis

Kozjak-Pavlovic, V, Ross, K, Benlasfer, N, Kimmig, S, Karlas, A, Rudel, T

EMBO Rep 2007
27479602 Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells

Anand, R, Strecker, V, Urbach, J, Wittig, I, Reichert, AS

PLoS ONE 2016
26477565 Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex

Huynen, MA, Mühlmeister, M, Gotthardt, K, Guerrero-Castillo, S, Brandt, U

Biochim. Biophys. Acta 2016
26968360 Distinct Roles of Mic12 and Mic27 in the Mitochondrial Contact Site and Cristae Organizing System

Zerbes, RM, Höß, P, Pfanner, N, van der Laan, M, Bohnert, M

J. Mol. Biol. 2016
17624330 The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11

Xie, J, Marusich, MF, Souda, P, Whitelegge, J, Capaldi, RA

FEBS Lett 2007
26416881 The Oxidation Status of Mic19 Regulates MICOS Assembly

Sakowska, P, Jans, DC, Mohanraj, K, Riedel, D, Jakobs, S, Chacinska, A

Mol. Cell. Biol. 2015
25997101 QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology

Guarani, V, McNeill, EM, Paulo, JA, Huttlin, EL, Fröhlich, F, Gygi, SP, Van Vactor, D, Harper, JW

Elife 2015
26530328 Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure

Ding, C, Wu, Z, Huang, L, Wang, Y, Xue, J, Chen, S, Deng, Z, Wang, L, Song, Z, Chen, S

Sci Rep 2015
22114354 MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization

Alkhaja, AK, Jans, DC, Nikolov, M, Vukotic, M, Lytovchenko, O, Ludewig, F, Schliebs, W, Riedel, D, Urlaub, H, Jakobs, S, Deckers, M

Mol. Biol. Cell 2012
24687277 Uniform nomenclature for the mitochondrial contact site and cristae organizing system

Pfanner, N, van der Laan, M, Amati, P, Capaldi, RA, Caudy, AA, Chacinska, A, Darshi, M, Deckers, M, Hoppins, S, Icho, T, Jakobs, S, Ji, J, Kozjak-Pavlovic, V, Meisinger, C, Odgren, PR, Park, SK, Rehling, P, Reichert, AS, Sheikh, MS, Taylor, SS, Tsuchida, N, van der Bliek, AM, van der Klei, IJ, Weissman, JS, Westermann, B, Zha, J, Neupert, W, Nunnari, J

J. Cell Biol. 2014
25764979 The non-glycosylated isoform of MIC26 is a constituent of the mammalian MICOS complex and promotes formation of crista junctions

Koob, S, Barrera, M, Anand, R, Reichert, AS

Biochim. Biophys. Acta 2015
27623147 QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease

Guarani, V, Jardel, C, Chrétien, D, Lombès, A, Bénit, P, Labasse, C, Lacène, E, Bourillon, A, Imbard, A, Benoist, JF, Dorboz, I, Gilleron, M, Goetzman, ES, Gaignard, P, Slama, A, Elmaleh-Bergès, M, Romero, NB, Rustin, P, Ogier de Baulny, H, Paulo, JA, Harper, JW, Schiff, M

Elife 2016
27485409 Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit

Zeharia, A, Friedman, JR, Tobar, A, Saada, A, Konen, O, Fellig, Y, Shaag, A, Nunnari, J, Elpeleg, O

Eur. J. Hum. Genet. 2016
25781180 Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits

Ott, C, Dorsch, E, Fraunholz, M, Straub, S, Kozjak-Pavlovic, V

PLoS ONE 2015
22252321 Sam50 functions in mitochondrial intermembrane space bridging and biogenesis of respiratory complexes

Ott, C, Ross, K, Straub, S, Thiede, B, Götz, M, Goosmann, C, Krischke, M, Mueller, MJ, Krohne, G, Rudel, T, Kozjak-Pavlovic, V

Mol. Cell. Biol. 2012
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