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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 | |||||||||
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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 / response to cobalamin / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / sperm glycocalyx / perinuclear theca ...response to D-galactosamine / Complex III assembly / response to cobalamin / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / blastocyst hatching / sperm glycocalyx / perinuclear theca / psychomotor behavior / Protein lipoylation / Mitochondrial Fatty Acid Beta-Oxidation / Complex I biogenesis / RHOG GTPase cycle / Mitochondrial ribosome-associated quality control / circulatory system development / Mitochondrial translation termination / Respiratory electron transport / response to mercury ion / mesenchymal stem cell differentiation / subthalamus development / pons development / protein insertion into mitochondrial inner membrane / response to light intensity / respiratory system process / cerebellar Purkinje cell layer development / : / mitochondrial respiratory chain complex III assembly / mitochondrial processing peptidase complex / sperm head-tail coupling apparatus / thalamus development / adult walking behavior / Mitochondrial protein degradation / pyramidal neuron development / stem cell division / response to alkaloid / response to glucagon / mitochondrial large ribosomal subunit assembly / mitochondrial ATP synthesis coupled electron transport / protein lipoylation / cellular response to oxygen levels / adult behavior / neural precursor cell proliferation / mitochondrial [2Fe-2S] assembly complex / mitochondrial large ribosomal subunit binding / ubiquinone biosynthetic process / respiratory chain complex / gliogenesis / respiratory chain complex III / negative regulation of non-canonical NF-kappaB signal transduction / cellular respiration / response to hydroperoxide / cardiac muscle tissue development / quinol-cytochrome-c reductase / oxidative phosphorylation / positive regulation of mitochondrial membrane potential / [2Fe-2S] cluster assembly / quinol-cytochrome-c reductase activity / oxygen sensor activity / sperm principal piece / cellular response to glucocorticoid stimulus / midbrain development / multicellular organism growth / mitochondrial electron transport, ubiquinol to cytochrome c / iron-sulfur cluster assembly / response to copper ion / hypothalamus development / dopamine metabolic process / sperm end piece / NADH:ubiquinone reductase (H+-translocating) / ubiquinone binding / animal organ regeneration / mitochondrial electron transport, NADH to ubiquinone / positive regulation of ATP biosynthetic process / proton motive force-driven mitochondrial ATP synthesis / neuron development / electron transport coupled proton transport / acyl binding / regulation of protein phosphorylation / mitochondrial respiratory chain complex I assembly / response to hyperoxia / response to cadmium ion / oxidoreductase activity, acting on NAD(P)H / NADH dehydrogenase activity / reactive oxygen species metabolic process / cerebellum development / respiratory chain complex I / positive regulation of execution phase of apoptosis / response to cAMP / NADH dehydrogenase (ubiquinone) activity / acyl carrier activity / neuron apoptotic process / extrinsic apoptotic signaling pathway / cellular response to interferon-beta / neurogenesis / quinone binding / cellular response to retinoic acid / ATP synthesis coupled electron transport / negative regulation of reactive oxygen species biosynthetic 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 | 88 KB 88 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 | 16.8 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-42122 ftp://ftp.pdbj.org/pub/emdb/structures/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 | ||||||||||||||||||||||||||||||||||||
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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

