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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 / subthalamus development ...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 / subthalamus development / pons development / Respiratory electron transport / protein insertion into mitochondrial inner membrane / response to cobalamin / cerebellar Purkinje cell layer development / blastocyst hatching / mitochondrial respiratory chain complex III assembly / pyramidal neuron development / respiratory system process / response to alkaloid / psychomotor behavior / cellular respiration / thalamus development / Mitochondrial protein degradation / cellular response to oxygen levels / response to light intensity / mesenchymal stem cell proliferation / respiratory chain complex / reproductive system development / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / gliogenesis / mesenchymal stem cell differentiation / circulatory system development / respiratory chain complex III / negative regulation of non-canonical NF-kappaB signal transduction / cardiac muscle tissue development / quinol-cytochrome-c reductase / neural precursor cell proliferation / [2Fe-2S] cluster assembly / response to glucagon / adult walking behavior / oxygen sensor activity / positive regulation of mitochondrial membrane potential / response to hydroperoxide / quinol-cytochrome-c reductase activity / cellular response to glucocorticoid stimulus / stem cell division / response to copper ion / mitochondrial electron transport, ubiquinol to cytochrome c / NADH dehydrogenase activity / iron-sulfur cluster assembly / hypothalamus development / midbrain development / electron transport coupled proton transport / dopamine metabolic process / mitochondrial ATP synthesis coupled electron transport / NADH:ubiquinone reductase (H+-translocating) / adult behavior / positive regulation of ATP biosynthetic process / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / respiratory chain complex I / positive regulation of execution phase of apoptosis / animal organ regeneration / response to hyperoxia / NADH dehydrogenase (ubiquinone) activity / response to cadmium ion / neuron development / quinone binding / cellular response to interferon-beta / ATP synthesis coupled electron transport / response to hormone / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / cellular response to retinoic acid / tricarboxylic acid cycle / neurogenesis / Neutrophil degranulation / visual perception / muscle contraction / reactive oxygen species metabolic process / 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 / fatty acid metabolic process / electron transport chain 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

