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-Structure paper
タイトル | The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 8248, Year 2023 |
掲載日 | 2023年12月12日 |
著者 | Lindsay McGregor / Samira Acajjaoui / Ambroise Desfosses / Melissa Saïdi / Maria Bacia-Verloop / Jennifer J Schwarz / Pauline Juyoux / Jill von Velsen / Matthew W Bowler / Andrew A McCarthy / Eaazhisai Kandiah / Irina Gutsche / Montserrat Soler-Lopez / |
PubMed 要旨 | The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer's ...The Mitochondrial Complex I Assembly (MCIA) complex is essential for the biogenesis of respiratory Complex I (CI), the first enzyme in the respiratory chain, which has been linked to Alzheimer's disease (AD) pathogenesis. However, how MCIA facilitates CI assembly, and how it is linked with AD pathogenesis, is poorly understood. Here we report the structural basis of the complex formation between the MCIA subunits ECSIT and ACAD9. ECSIT binding induces a major conformational change in the FAD-binding loop of ACAD9, releasing the FAD cofactor and converting ACAD9 from a fatty acid β-oxidation (FAO) enzyme to a CI assembly factor. We provide evidence that ECSIT phosphorylation downregulates its association with ACAD9 and is reduced in neuronal cells upon exposure to amyloid-β (Aβ) oligomers. These findings advance our understanding of the MCIA complex assembly and suggest a possible role for ECSIT in the reprogramming of bioenergetic pathways linked to Aβ toxicity, a hallmark of AD. |
リンク | Nat Commun / PubMed:38086790 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 6.0 Å |
構造データ | EMDB-17659, PDB-8phe: EMDB-17660, PDB-8phf: EMDB-17661: ACAD9 homodimer WT |
化合物 | ChemComp-HOH: ChemComp-FAD: |
由来 |
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キーワード | SIGNALING PROTEIN / Oxidative phosphorylation (OXPHOS) / Fatty Acid Oxidation (FAO) / Mitochondrial Complex I Assembly Complex (MCIA) / Amyloid-beta / ECSIT phosphorylation / FLAVOPROTEIN |