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Yorodumi- EMDB-42122: Formation of I2+III2 supercomplex rescues respiratory chain defects -
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Open data
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Basic information
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| Title | Formation of I2+III2 supercomplex rescues respiratory chain defects | |||||||||
Map data | Composite map | |||||||||
Sample |
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Keywords | Super complex XL (CI2+CIII2) / ELECTRON TRANSPORT / Translocase | |||||||||
| Function / homology | Function and homology informationresponse to D-galactosamine / Complex III assembly / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / response to mercury ion / Respiratory electron transport ...response to D-galactosamine / Complex III assembly / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / response to mercury ion / Respiratory electron transport / protein insertion into mitochondrial inner membrane / subthalamus development / pons development / response to cobalamin / cerebellar Purkinje cell layer development / blastocyst hatching / mitochondrial respiratory chain complex III assembly / respiratory system process / psychomotor behavior / pyramidal neuron development / response to alkaloid / cellular respiration / Mitochondrial protein degradation / thalamus development / response to light intensity / iron-sulfur cluster assembly complex / cellular response to oxygen levels / mesenchymal stem cell proliferation / reproductive system development / mitochondrial large ribosomal subunit binding / respiratory chain complex / gliogenesis / mitochondrial [2Fe-2S] assembly complex / respiratory chain complex III / mesenchymal stem cell differentiation / circulatory system development / negative regulation of non-canonical NF-kappaB signal transduction / quinol-cytochrome-c reductase / response to glucagon / adult walking behavior / cardiac muscle tissue development / positive regulation of mitochondrial membrane potential / response to hydroperoxide / neural precursor cell proliferation / [2Fe-2S] cluster assembly / oxygen sensor activity / quinol-cytochrome-c reductase activity / cellular response to glucocorticoid stimulus / response to copper ion / stem cell division / NADH dehydrogenase activity / mitochondrial electron transport, ubiquinol to cytochrome c / iron-sulfur cluster assembly / hypothalamus development / midbrain development / electron transport coupled proton transport / dopamine metabolic process / adult behavior / NADH:ubiquinone reductase (H+-translocating) / mitochondrial ATP synthesis coupled electron transport / positive regulation of ATP biosynthetic process / mitochondrial respiratory chain complex I assembly / proton motive force-driven mitochondrial ATP synthesis / mitochondrial electron transport, NADH to ubiquinone / response to hyperoxia / animal organ regeneration / respiratory chain complex I / positive regulation of execution phase of apoptosis / response to cadmium ion / NADH dehydrogenase (ubiquinone) activity / neuron development / quinone binding / cellular response to interferon-beta / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic process / response to hormone / extrinsic apoptotic signaling pathway / cellular response to retinoic acid / tricarboxylic acid cycle / neurogenesis / Neutrophil degranulation / visual perception / reactive oxygen species metabolic process / muscle contraction / aerobic respiration / cerebellum development / response to activity / regulation of mitochondrial membrane potential / respiratory electron transport chain / response to nicotine / response to cocaine / mitochondrion organization / hippocampus development / DNA damage response, signal transduction by p53 class mediator / kidney development / response to hydrogen peroxide / monooxygenase activity / sensory perception of sound / electron transport chain / fatty acid metabolic process Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Letts JA / Padavannil A | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Cell Metab / Year: 2025Title: Formation of I+III supercomplex rescues respiratory chain defects. Authors: Chao Liang / Abhilash Padavannil / Shan Zhang / Sheryl Beh / David R L Robinson / Jana Meisterknecht / Alfredo Cabrera-Orefice / Timothy R Koves / Chika Watanabe / Miyuki Watanabe / María ...Authors: Chao Liang / Abhilash Padavannil / Shan Zhang / Sheryl Beh / David R L Robinson / Jana Meisterknecht / Alfredo Cabrera-Orefice / Timothy R Koves / Chika Watanabe / Miyuki Watanabe / María Illescas / Radiance Lim / Jordan M Johnson / Shuxun Ren / Ya-Jun Wu / Dennis Kappei / Anna Maria Ghelli / Katsuhiko Funai / Hitoshi Osaka / Deborah Muoio / Cristina Ugalde / Ilka Wittig / David A Stroud / James A Letts / Lena Ho / ![]() Abstract: Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the ...Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.7 Å by cryoelectron microscopy (cryo-EM). SC-XL formation increases mitochondrial cristae density, reduces CIII reactive oxygen species (ROS), and sustains normal respiration despite a 70% reduction in CIII activity, effectively rescuing CIII deficiency. Consequently, inhibiting SC-XL formation in CIII mutants using the Uqcrc1 contact site mutation leads to respiratory decompensation. Lastly, SC-XL formation promotes fatty acid oxidation (FAO) and protects against ischemic heart failure in mice. Our study uncovers an unexpected plasticity in the mammalian ETC, where structural adaptations mitigate intrinsic perturbations, and suggests that manipulating SC-XL formation is a potential therapeutic strategy for mitochondrial dysfunction. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_42122.map.gz | 103.8 MB | EMDB map data format | |
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| Header (meta data) | emd-42122-v30.xml emd-42122.xml | 82.1 KB 82.1 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_42122_fsc.xml | 22.4 KB | Display | FSC data file |
| Images | emd_42122.png | 151.7 KB | ||
| Filedesc metadata | emd-42122.cif.gz | 16.4 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42122 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-42122 | HTTPS FTP |
-Validation report
| Summary document | emd_42122_validation.pdf.gz | 569.7 KB | Display | EMDB validaton report |
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| Full document | emd_42122_full_validation.pdf.gz | 569.3 KB | Display | |
| Data in XML | emd_42122_validation.xml.gz | 4.5 KB | Display | |
| Data in CIF | emd_42122_validation.cif.gz | 5.1 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42122 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-42122 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8ucaMC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_42122.map.gz / Format: CCP4 / Size: 113 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | Composite map | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.88 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Mitochondrial Super-complex with CI dimer and CIII dimer (Super-c...
+Supramolecule #1: Mitochondrial Super-complex with CI dimer and CIII dimer (Super-c...
+Macromolecule #1: NADH-ubiquinone oxidoreductase chain 3
+Macromolecule #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+Macromolecule #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+Macromolecule #4: NADH-ubiquinone oxidoreductase chain 1
+Macromolecule #5: NADH-ubiquinone oxidoreductase chain 6
+Macromolecule #6: NADH-ubiquinone oxidoreductase chain 4L
+Macromolecule #7: NADH-ubiquinone oxidoreductase chain 5
+Macromolecule #8: NADH-ubiquinone oxidoreductase chain 4
+Macromolecule #9: NADH-ubiquinone oxidoreductase chain 2
+Macromolecule #10: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+Macromolecule #11: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+Macromolecule #12: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
+Macromolecule #13: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+Macromolecule #14: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+Macromolecule #15: Acyl carrier protein, mitochondrial
+Macromolecule #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+Macromolecule #17: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+Macromolecule #18: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+Macromolecule #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11
+Macromolecule #20: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+Macromolecule #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+Macromolecule #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+Macromolecule #23: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+Macromolecule #24: NADH dehydrogenase [ubiquinone] 1 subunit C2
+Macromolecule #25: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+Macromolecule #26: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+Macromolecule #27: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+Macromolecule #28: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+Macromolecule #29: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+Macromolecule #30: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+Macromolecule #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+Macromolecule #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+Macromolecule #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+Macromolecule #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+Macromolecule #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+Macromolecule #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+Macromolecule #37: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+Macromolecule #38: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+Macromolecule #39: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+Macromolecule #40: Cytochrome b-c1 complex subunit 1, mitochondrial
+Macromolecule #41: Cytochrome b-c1 complex subunit 2, mitochondrial
+Macromolecule #42: Cytochrome b
+Macromolecule #43: Cytochrome c1, heme protein, mitochondrial
+Macromolecule #44: Cytochrome b-c1 complex subunit 9
+Macromolecule #45: Cytochrome b-c1 complex subunit 7
+Macromolecule #46: Cytochrome b-c1 complex subunit 8
+Macromolecule #47: Cytochrome b-c1 complex subunit 6, mitochondrial
+Macromolecule #48: Cytochrome b-c1 complex subunit 9
+Macromolecule #49: Cytochrome b-c1 complex subunit 10
+Macromolecule #50: Cytochrome b-c1 complex subunit Rieske, mitochondrial
+Macromolecule #51: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+Macromolecule #52: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+Macromolecule #53: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+Macromolecule #54: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+Macromolecule #55: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+Macromolecule #56: MAGNESIUM ION
+Macromolecule #57: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE
+Macromolecule #58: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+Macromolecule #59: ZINC ION
+Macromolecule #60: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
+Macromolecule #61: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #62: HEME C
+Macromolecule #63: FLAVIN MONONUCLEOTIDE
+Macromolecule #64: IRON/SULFUR CLUSTER
+Macromolecule #65: FE2/S2 (INORGANIC) CLUSTER
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.7 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
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Keywords
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

