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

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

Stable Identifier

R-HSA-8949609

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

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

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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