Cristae formation (Homo sapiens)

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1, 6, 15, 18, 21...4, 5, 7-9, 11...3, 10, 14, 16, 20...mitochondrial matrixmitochondrial intermembrane spaceATP5I ATP5G3 ATP5G2 ATP5H ATP5C1 ATP5S ATP5H ATP5F1 ATP5S CHCHD6 (MIC25) CHCHD3 (MIC19)ATP5G1 ATP5D MIBMT-ATP6 MT-ATP6 MINOS1 (MIC10) ATP5A1 ATP5L IMMT (MIC60) SAM complexATP5C1 ATP5G2 MT-ATP8 MT-ATP8 ATP5J CHCHD6 (MIC25)ATP5J2 APOO (MIC26)ATP5L HSPA9(1-679)ATP5B IMMT (MIC60)ATP5J2 ATP5D APOO (MIC26) TMEM11 CHCHD3 (MIC19) DNAJC11 F1Fo ATP synthasedimerSAMM50 ATP5G1 ATP5E ATP5I ATP5E MTX1 SAMM50 MTX2 ATP5A1 APOOL (MIC27) ATP5O DNAJC11MTX2 APOOL (MIC27)ATP5G3 ATP5O TMEM11MINOS1 (MIC10)ATP5F1 F1Fo ATP synthaseHSPA9(1-679) ATP5J ATP5B MIC13 (QIL1)MTX1 MIC13 (QIL1) 2, 2213, 238, 11, 13, 2314


Cristae are invaginations of the inner mitochondrial membrane that extend into the matrix and are lined with cytochrome complexes and F1Fo ATP synthase complexes. Cristae increase the surface area of the inner membranes allowing greater numbers of respiratory complexes. Cristae are also believed to serve as "proton pockets" to generate localized regions of higher membrane potential. The steps in the biogenesis of cristae are not yet completely elucidated (reviewed in Zick et al. 2009) but the formation of the Mitochondrial Contact Site and Cristae Organizing System (MICOS, formerly also known as MINOS, reviewed in Rampelt et al. 2016, Kozjak-Pavlovic 2016, van der Laan et al. 2016) and localized concentrations of cardiolipin are known to define the inward curvature of the inner membrane at the bases of cristae. MICOS also links these regions of the inner membrane with complexes (the SAM complex and, in fungi, the TOM complex) embedded in the outer membrane. CHCHD3 (MIC19) and IMMT (MIC60) subunits of MICOS also interact with OPA1 at the inner membrane (Darshi et al. 2011, Glytsou et al. 2016).
Formation of dimers or oligomers of the F1Fo ATP synthase complex causes extreme curvature of the inner membrane at the apices of cristae (reviewed in Seelert and Dencher 2011, Habersetzer et al. 2013). Defects in either MICOS or F1Fo ATP synthase oligomerization produce abnormal mitochondrial morphologies. View original pathway at Reactome.


Pathway is converted from Reactome ID: 8949613
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Reactome Author: May, Bruce

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  1. Glytsou C, Calvo E, Cogliati S, Mehrotra A, Anastasia I, Rigoni G, Raimondi A, Shintani N, Loureiro M, Vazquez J, Pellegrini L, Enriquez JA, Scorrano L, Soriano ME.; ''Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control.''; PubMed Europe PMC Scholia
  2. Habersetzer J, Ziani W, Larrieu I, Stines-Chaumeil C, Giraud MF, Brèthes D, Dautant A, Paumard P.; ''ATP synthase oligomerization: from the enzyme models to the mitochondrial morphology.''; PubMed Europe PMC Scholia
  3. Ott C, Dorsch E, Fraunholz M, Straub S, Kozjak-Pavlovic V.; ''Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits.''; PubMed Europe PMC Scholia
  4. Alkhaja AK, Jans DC, Nikolov M, Vukotic M, Lytovchenko O, Ludewig F, Schliebs W, Riedel D, Urlaub H, Jakobs S, Deckers M.; ''MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization.''; PubMed Europe PMC Scholia
  5. Anand R, Strecker V, Urbach J, Wittig I, Reichert AS.; ''Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.''; PubMed Europe PMC Scholia
  6. Kozjak-Pavlovic V, Ross K, Benlasfer N, Kimmig S, Karlas A, Rudel T.; ''Conserved roles of Sam50 and metaxins in VDAC biogenesis.''; PubMed Europe PMC Scholia
  7. 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.; ''QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease.''; PubMed Europe PMC Scholia
  8. Davies KM, Daum B, Gold VA, Mühleip AW, Brandt T, Blum TB, Mills DJ, Kühlbrandt W.; ''Visualization of ATP synthase dimers in mitochondria by electron cryo-tomography.''; PubMed Europe PMC Scholia
  9. Davies KM, Davies KM, Strauss M, Daum B, Kief JH, Osiewacz HD, Rycovska A, Zickermann V, Kühlbrandt W.; ''Macromolecular organization of ATP synthase and complex I in whole mitochondria.''; PubMed Europe PMC Scholia
  10. Sakowska P, Jans DC, Mohanraj K, Riedel D, Jakobs S, Chacinska A.; ''The Oxidation Status of Mic19 Regulates MICOS Assembly.''; PubMed Europe PMC Scholia
  11. Ott C, Ross K, Straub S, Thiede B, Götz M, Goosmann C, Krischke M, Mueller MJ, Krohne G, Rudel T, Kozjak-Pavlovic V.; ''Sam50 functions in mitochondrial intermembrane space bridging and biogenesis of respiratory complexes.''; PubMed Europe PMC Scholia
  12. Zerbes RM, Höß P, Pfanner N, van der Laan M, Bohnert M.; ''Distinct Roles of Mic12 and Mic27 in the Mitochondrial Contact Site and Cristae Organizing System.''; PubMed Europe PMC Scholia
  13. Guarani V, McNeill EM, Paulo JA, Huttlin EL, Fröhlich F, Gygi SP, Van Vactor D, Harper JW.; ''QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology.''; PubMed Europe PMC Scholia
  14. Strauss M, Hofhaus G, Schröder RR, Kühlbrandt W.; ''Dimer ribbons of ATP synthase shape the inner mitochondrial membrane.''; PubMed Europe PMC Scholia
  15. Davies KM, Anselmi C, Wittig I, Faraldo-Gómez JD, Kühlbrandt W.; ''Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae.''; PubMed Europe PMC Scholia
  16. Couoh-Cardel SJ, Uribe-Carvajal S, Wilkens S, García-Trejo JJ.; ''Structure of dimeric F1F0-ATP synthase.''; PubMed Europe PMC Scholia
  17. Rampelt H, Zerbes RM, van der Laan M, Pfanner N.; ''Role of the mitochondrial contact site and cristae organizing system in membrane architecture and dynamics.''; PubMed Europe PMC Scholia
  18. Zick M, Rabl R, Reichert AS.; ''Cristae formation-linking ultrastructure and function of mitochondria.''; PubMed Europe PMC Scholia
  19. Darshi M, Mendiola VL, Mackey MR, Murphy AN, Koller A, Perkins GA, Ellisman MH, Taylor SS.; ''ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function.''; PubMed Europe PMC Scholia
  20. Koob S, Barrera M, Anand R, Reichert AS.; ''The non-glycosylated isoform of MIC26 is a constituent of the mammalian MICOS complex and promotes formation of crista junctions.''; PubMed Europe PMC Scholia
  21. Seelert H, Dencher NA.; ''ATP synthase superassemblies in animals and plants: two or more are better.''; PubMed Europe PMC Scholia
  22. Habersetzer J, Larrieu I, Priault M, Salin B, Rossignol R, Brèthes D, Paumard P.; ''Human F1F0 ATP synthase, mitochondrial ultrastructure and OXPHOS impairment: a (super-)complex matter?''; PubMed Europe PMC Scholia
  23. Xie J, Marusich MF, Souda P, Whitelegge J, Capaldi RA.; ''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.''; PubMed Europe PMC Scholia
  24. Belogrudov GI.; ''Factor B is essential for ATP synthesis by mitochondria.''; PubMed Europe PMC Scholia
  25. Cortés-Hernández P, Vázquez-Memije ME, García JJ.; ''ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization.''; PubMed Europe PMC Scholia
  26. Ding C, Wu Z, Huang L, Wang Y, Xue J, Chen S, Deng Z, Wang L, Song Z, Chen S.; ''Mitofilin and CHCHD6 physically interact with Sam50 to sustain cristae structure.''; PubMed Europe PMC Scholia
  27. Huynen MA, Mühlmeister M, Gotthardt K, Guerrero-Castillo S, Brandt U.; ''Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.''; PubMed Europe PMC Scholia
  28. Belogrudov GI, Hatefi Y.; ''Factor B and the mitochondrial ATP synthase complex.''; PubMed Europe PMC Scholia
  29. Kozjak-Pavlovic V.; ''The MICOS complex of human mitochondria.''; PubMed Europe PMC Scholia
  30. 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.; ''Uniform nomenclature for the mitochondrial contact site and cristae organizing system.''; PubMed Europe PMC Scholia
  31. Zeharia A, Friedman JR, Tobar A, Saada A, Konen O, Fellig Y, Shaag A, Nunnari J, Elpeleg O.; ''Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit.''; PubMed Europe PMC Scholia
  32. van der Laan M, Horvath SE, Pfanner N.; ''Mitochondrial contact site and cristae organizing system.''; PubMed Europe PMC Scholia


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101112view21:28, 31 October 2018ReactomeTeamreactome version 65
100640view20:02, 31 October 2018ReactomeTeamreactome version 64
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93562view11:27, 9 August 2017ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
APOO (MIC26) ProteinQ9BUR5 (Uniprot-TrEMBL)
APOO (MIC26)ProteinQ9BUR5 (Uniprot-TrEMBL)
APOOL (MIC27) ProteinQ6UXV4 (Uniprot-TrEMBL)
APOOL (MIC27)ProteinQ6UXV4 (Uniprot-TrEMBL)
ATP5A1 ProteinP25705 (Uniprot-TrEMBL)
ATP5B ProteinP06576 (Uniprot-TrEMBL)
ATP5C1 ProteinP36542 (Uniprot-TrEMBL)
ATP5D ProteinP30049 (Uniprot-TrEMBL)
ATP5E ProteinP56381 (Uniprot-TrEMBL)
ATP5F1 ProteinP24539 (Uniprot-TrEMBL)
ATP5G1 ProteinP05496 (Uniprot-TrEMBL)
ATP5G2 ProteinQ06055 (Uniprot-TrEMBL)
ATP5G3 ProteinP48201 (Uniprot-TrEMBL)
ATP5H ProteinO75947 (Uniprot-TrEMBL)
ATP5I ProteinP56385 (Uniprot-TrEMBL)
ATP5J ProteinP18859 (Uniprot-TrEMBL)
ATP5J2 ProteinP56134 (Uniprot-TrEMBL)
ATP5L ProteinO75964 (Uniprot-TrEMBL)
ATP5O ProteinP48047 (Uniprot-TrEMBL)
ATP5S ProteinQ99766 (Uniprot-TrEMBL)
CHCHD3 (MIC19) ProteinQ9NX63 (Uniprot-TrEMBL)
CHCHD3 (MIC19)ProteinQ9NX63 (Uniprot-TrEMBL)
CHCHD6 (MIC25) ProteinQ9BRQ6 (Uniprot-TrEMBL)
CHCHD6 (MIC25)ProteinQ9BRQ6 (Uniprot-TrEMBL)
DNAJC11 ProteinQ9NVH1 (Uniprot-TrEMBL)
DNAJC11ProteinQ9NVH1 (Uniprot-TrEMBL)
F1Fo ATP synthase dimerComplexR-HSA-8949570 (Reactome)
F1Fo ATP synthaseComplexR-HSA-74186 (Reactome) Mitochondrial ATP synthase subunit s (ATP5S) appears to be an essential subunit necessary for H+ conduction of ATP synthase (Belogrudov & Hatefi 2002, Belogrudov 2002).
HSPA9(1-679) ProteinP38646 (Uniprot-TrEMBL)
HSPA9(1-679)ProteinP38646 (Uniprot-TrEMBL)
IMMT (MIC60) ProteinQ16891 (Uniprot-TrEMBL)
IMMT (MIC60)ProteinQ16891 (Uniprot-TrEMBL)
MIBComplexR-HSA-8949617 (Reactome)
MIC13 (QIL1) ProteinQ5XKP0 (Uniprot-TrEMBL)
MIC13 (QIL1)ProteinQ5XKP0 (Uniprot-TrEMBL)
MINOS1 (MIC10) ProteinQ5TGZ0 (Uniprot-TrEMBL)
MINOS1 (MIC10)ProteinQ5TGZ0 (Uniprot-TrEMBL)
MT-ATP6 ProteinP00846 (Uniprot-TrEMBL)
MT-ATP8 ProteinP03928 (Uniprot-TrEMBL)
MTX1 ProteinQ13505 (Uniprot-TrEMBL)
MTX2 ProteinO75431 (Uniprot-TrEMBL)
SAM complexComplexR-HSA-1252247 (Reactome) The SAM complex is inferred from homologous subunits in Saccharomyces cerevisiae. Xie et al. (2007) found human SAM50 in a complex with metaxin 1, metaxin 2, mitofilin, CHCHD3, CHCHD6, and DnaJC1 however Kozjak-Pavlovic et al. (2007) found SAM50 in a separate complex from the metaxins.
SAMM50 ProteinQ9Y512 (Uniprot-TrEMBL)
TMEM11 ProteinP17152 (Uniprot-TrEMBL)
TMEM11ProteinP17152 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
APOO (MIC26)R-HSA-8949609 (Reactome)
APOOL (MIC27)R-HSA-8949609 (Reactome)
CHCHD3 (MIC19)R-HSA-8949609 (Reactome)
CHCHD6 (MIC25)R-HSA-8949609 (Reactome)
DNAJC11R-HSA-8949609 (Reactome)
F1Fo ATP synthase dimerArrowR-HSA-8949580 (Reactome)
F1Fo ATP synthaseR-HSA-8949580 (Reactome)
HSPA9(1-679)R-HSA-8949609 (Reactome)
IMMT (MIC60)R-HSA-8949609 (Reactome)
MIBArrowR-HSA-8949609 (Reactome)
MIC13 (QIL1)R-HSA-8949609 (Reactome)
MINOS1 (MIC10)R-HSA-8949609 (Reactome)
R-HSA-8949580 (Reactome) At the inner mitochondrial membrane, an F1Fo ATP synthase complex binds another F1Fo ATP synthase complex to form a dimer that causes curvature of the inner mitochondrial membrane at internal regions of cristae (Habersetzer et al. 2013, inferred from bovine homologs in Strauss et al. 2008, Davies et al. 2011, Davies et al. 2012, inferred from yeast homologs in Arnold et al. 1998, Couoh-Cardel et al. 2010). The dimers are observed in rows along the highly curved apices of cristae (inferred from bovine homologs in Davies et al. 2014).
R-HSA-8949609 (Reactome) 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).
SAM complexR-HSA-8949609 (Reactome)
TMEM11R-HSA-8949609 (Reactome)
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