PXD042858

PXD042858 is an original dataset announced via ProteomeXchange.

Title	The structural mechanism of MCIA complex assembly links mitochondrial redox pathways
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:17:33.223.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Schwarz
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-09 12:13:51	ID requested
1	2023-12-13 08:22:37	announced
⏵ 2	2024-10-22 06:17:33	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Oxidative phosphorylation (OXPHOS), Mitochondrial Complex I Assembly Complex (MCIA), Fatty Acid Oxidation (FAO), Amyloid-β, ECSIT phosphorylation, Cryo-EM

Montserrat Soler-Lopez
contact affiliation	Structural Biology Group, European Synchrotron Radiation Facility (ESRF), Grenoble, France
contact email	montserrat.soler-lopez@esrf.fr
lab head
Jennifer Schwarz
contact affiliation	European Molecular Biology Laboratory, Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
contact email	jennifer.schwarz@embl.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/12/PXD042858

PRIDE project URI

• PRIDE
  1. PXD042858
     1. Label: PRIDE project
     2. Name: The structural mechanism of MCIA complex assembly links mitochondrial redox pathways