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-Structure paper
タイトル | Structural basis for a complex I mutation that blocks pathological ROS production. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 707, Year 2021 |
掲載日 | 2021年1月29日 |
著者 | Zhan Yin / Nils Burger / Duvaraka Kula-Alwar / Dunja Aksentijević / Hannah R Bridges / Hiran A Prag / Daniel N Grba / Carlo Viscomi / Andrew M James / Amin Mottahedin / Thomas Krieg / Michael P Murphy / Judy Hirst / |
PubMed 要旨 | Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease- ...Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury. |
リンク | Nat Commun / PubMed:33514727 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.17 - 3.82 Å |
構造データ | EMDB-11810, PDB-7ak5: EMDB-11811, PDB-7ak6: |
化合物 | ChemComp-SF4: ChemComp-PC1: ChemComp-FES: ChemComp-FMN: ChemComp-3PE: ChemComp-CDL: ChemComp-ATP: ChemComp-NDP: ChemComp-ZN: ChemComp-EHZ: |
由来 |
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キーワード | OXIDOREDUCTASE / deactive complex I / Complex I with mutation |