Cristae formation (Homo sapiens)

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2, 11, 13, 14, 19...3, 9, 15, 16, 18...1, 5-7, 10...mitochondrial matrixmitochondrial intermembrane spaceATP5E ATP5B ATP5C1 TMEM11ATP5G3 TMEM11 ATP5E ATP5J2 ATP5L ATP5C1 MTX1 F1Fo ATP synthasedimerATP5D ATP5G2 MTX2 ATP5B MT-ATP6 ATP5O MTX1 ATP5L ATP5I MINOS1 (MIC10) SAMM50 DNAJC11APOOL (MIC27) ATP5I ATP5H ATP5S MT-ATP8 ATP5A1 ATP5J IMMT (MIC60) APOOL (MIC27)ATP5J MINOS1 (MIC10)SAM complexAPOO (MIC26)CHCHD6 (MIC25)ATP5F1 CHCHD3 (MIC19)ATP5G1 ATP5O MIBATP5G2 MIC13 (QIL1) MTX2 ATP5H HSPA9(1-679) CHCHD6 (MIC25) ATP5A1 MT-ATP8 ATP5J2 APOO (MIC26) ATP5F1 ATP5D MIC13 (QIL1)ATP5G1 SAMM50 ATP5S IMMT (MIC60)DNAJC11 CHCHD3 (MIC19) ATP5G3 HSPA9(1-679)MT-ATP6 F1Fo ATP synthase6, 234, 86, 7, 20, 2316


Description

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.

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Reactome-Converter 
Pathway is converted from Reactome ID: 8949613
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Reactome version: 62
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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History

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115015view16:55, 25 January 2021ReactomeTeamReactome version 75
113460view11:53, 2 November 2020ReactomeTeamReactome version 74
112660view16:04, 9 October 2020ReactomeTeamReactome version 73
101576view11:44, 1 November 2018ReactomeTeamreactome version 66
101112view21:28, 31 October 2018ReactomeTeamreactome version 65
100640view20:02, 31 October 2018ReactomeTeamreactome version 64
100190view16:46, 31 October 2018ReactomeTeamreactome version 63
99740view15:13, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93562view11:27, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
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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