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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Formation of I2+III2 supercomplex rescues respiratory chain defects | |||||||||
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![]() | Super complex XL (CI2+CIII2) / ELECTRON TRANSPORT / Translocase | |||||||||
機能・相同性 | ![]() response to D-galactosamine / Complex III assembly / subthalamus development / pons development / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / cerebellar Purkinje cell layer development / Protein lipoylation ...response to D-galactosamine / Complex III assembly / subthalamus development / pons development / Mitochondrial protein import / response to injury involved in regulation of muscle adaptation / mesenchymal stem cell proliferation / reproductive system development / cerebellar Purkinje cell layer development / 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 / mesenchymal stem cell differentiation / circulatory system development / pyramidal neuron development / blastocyst hatching / thalamus development / mitochondrial respiratory chain complex III assembly / respiratory system process / psychomotor behavior / cellular respiration / Mitochondrial protein degradation / cellular response to oxygen levels / stem cell division / respiratory chain complex / response to light intensity / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit binding / response to copper ion / gliogenesis / response to alkaloid / respiratory chain complex III / negative regulation of non-canonical NF-kappaB signal transduction / response to glucagon / cardiac muscle tissue development / neural precursor cell proliferation / quinol-cytochrome-c reductase / positive regulation of mitochondrial membrane potential / [2Fe-2S] cluster assembly / adult walking behavior / cellular response to glucocorticoid stimulus / oxygen sensor activity / quinol-cytochrome-c reductase activity / response to hydroperoxide / mitochondrial electron transport, ubiquinol to cytochrome c / hypothalamus development / iron-sulfur cluster assembly / positive regulation of ATP biosynthetic process / midbrain development / response to cobalamin / electron transport coupled proton transport / dopamine metabolic process / adult behavior / NADH:ubiquinone reductase (H+-translocating) / mitochondrial respiratory chain complex I assembly / positive regulation of execution phase of apoptosis / mitochondrial electron transport, NADH to ubiquinone / NADH dehydrogenase activity / proton motive force-driven mitochondrial ATP synthesis / respiratory chain complex I / response to hyperoxia / NADH dehydrogenase (ubiquinone) activity / neuron development / animal organ regeneration / quinone binding / cellular response to interferon-beta / response to cadmium ion / ATP synthesis coupled electron transport / cellular response to retinoic acid / negative regulation of reactive oxygen species biosynthetic process / extrinsic apoptotic signaling pathway / response to hormone / neurogenesis / tricarboxylic acid cycle / muscle contraction / Neutrophil degranulation / visual perception / cerebellum development / reactive oxygen species metabolic process / aerobic respiration / DNA damage response, signal transduction by p53 class mediator / regulation of mitochondrial membrane potential / hippocampus development / response to activity / kidney development / fatty acid metabolic process / respiratory electron transport chain / mitochondrion organization / response to nicotine / sensory perception of sound / response to cocaine / monooxygenase activity / electron transport chain / mitochondrial membrane / brain development 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.7 Å | |||||||||
![]() | Letts JA / Padavannil A | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Formation of I+III supercomplex rescues respiratory chain defects. 著者: 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 ...著者: 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() 要旨: 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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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 103.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 82.1 KB 82.1 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 22.4 KB | 表示 | ![]() |
画像 | ![]() | 151.7 KB | ||
Filedesc metadata | ![]() | 16.4 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8ucaMC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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注釈 | Composite map | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 これらの図は立方格子座標系で作成されたものです | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.88 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Mitochondrial Super-complex with CI dimer and CIII dimer (Super-c...
+超分子 #1: Mitochondrial Super-complex with CI dimer and CIII dimer (Super-c...
+分子 #1: NADH-ubiquinone oxidoreductase chain 3
+分子 #2: NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial
+分子 #3: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
+分子 #4: NADH-ubiquinone oxidoreductase chain 1
+分子 #5: NADH-ubiquinone oxidoreductase chain 6
+分子 #6: NADH-ubiquinone oxidoreductase chain 4L
+分子 #7: NADH-ubiquinone oxidoreductase chain 5
+分子 #8: NADH-ubiquinone oxidoreductase chain 4
+分子 #9: NADH-ubiquinone oxidoreductase chain 2
+分子 #10: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mi...
+分子 #11: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mit...
+分子 #12: NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
+分子 #13: NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
+分子 #14: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2
+分子 #15: Acyl carrier protein, mitochondrial
+分子 #16: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5
+分子 #17: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6
+分子 #18: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8
+分子 #19: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11
+分子 #20: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
+分子 #21: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
+分子 #22: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
+分子 #23: NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
+分子 #24: NADH dehydrogenase [ubiquinone] 1 subunit C2
+分子 #25: NADH dehydrogenase [ubiquinone] iron-sulfur protein 5
+分子 #26: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
+分子 #27: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mit...
+分子 #28: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mito...
+分子 #29: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
+分子 #30: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mito...
+分子 #31: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3
+分子 #32: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mito...
+分子 #33: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
+分子 #34: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9
+分子 #35: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
+分子 #36: NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10
+分子 #37: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12
+分子 #38: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
+分子 #39: NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
+分子 #40: Cytochrome b-c1 complex subunit 1, mitochondrial
+分子 #41: Cytochrome b-c1 complex subunit 2, mitochondrial
+分子 #42: Cytochrome b
+分子 #43: Cytochrome c1, heme protein, mitochondrial
+分子 #44: Cytochrome b-c1 complex subunit 9
+分子 #45: Cytochrome b-c1 complex subunit 7
+分子 #46: Cytochrome b-c1 complex subunit 8
+分子 #47: Cytochrome b-c1 complex subunit 6, mitochondrial
+分子 #48: Cytochrome b-c1 complex subunit 9
+分子 #49: Cytochrome b-c1 complex subunit 10
+分子 #50: Cytochrome b-c1 complex subunit Rieske, mitochondrial
+分子 #51: NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
+分子 #52: NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
+分子 #53: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
+分子 #54: NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
+分子 #55: NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial
+分子 #56: MAGNESIUM ION
+分子 #57: 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE
+分子 #58: NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
+分子 #59: ZINC ION
+分子 #60: ~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butan...
+分子 #61: PROTOPORPHYRIN IX CONTAINING FE
+分子 #62: HEME C
+分子 #63: FLAVIN MONONUCLEOTIDE
+分子 #64: IRON/SULFUR CLUSTER
+分子 #65: FE2/S2 (INORGANIC) CLUSTER
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.7 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS GLACIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: ![]() |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.5 µm |