EMD-17660

Single-particle
3.6 Å
EMD-17660 Deposition: 19/06/2023
Map released: 24/01/2024
Last modified: 31/01/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-17660

Cryo-EM structure of human ACAD9-S191A

EMD-17660

Single-particle
3.6 Å
EMD-17660 Deposition: 19/06/2023
Map released: 24/01/2024
Last modified: 31/01/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: ACAD9 S191A
Fitted models: 8phf (Avg. Q-score: 0.418)

Deposition Authors: McGregor L , Acajjaoui S, Desfosses A , Saidi M, Bacia-Verloop M, Schwarz JJ, Juyoux P , Von Velsen J, Bowler MW , McCarthy A, Kandiah E , Gutsche I , Soler-Lopez M
The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination.
PUBMED: 38086790
DOI: doi:10.1038/s41467-023-43865-0
ISSN: 2041-1723
Abstract:
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.