PXD064658

PXD064658 is an original dataset announced via ProteomeXchange.

Title	Complex II assembly drives metabolic adaptation to OXPHOS dysfunction
Description	During acute oxidative phosphorylation (OXPHOS) dysfunction, the reverse activity of succinate dehydrogenase (Complex II) maintains the redox state of the Coenzyme Q pool by utilizing either fumarate or oxygen as terminal electron acceptors. The tendency for one over another has been suggested to be tissue specific. We identified the action of SDHAF2 protein, a Complex II assembly factor that enhances the flavination of catalytic subunit SDHA, as critical for metabolic adaptation during Complex III dysfunction in HEK293T cells. Loss of SDHAF2 during Complex III inhibition led to a net reductive TCA cycle from loss of succinate oxidation, loss of SDHA active site derived reactive oxygen species (ROS)-signaling, insufficient adaptation to glycolysis, and a severe growth impairment. Cell lines adapted to glycolysis did not accumulate SDHAF2 upon Coenzyme Q-pool stress, exhibited a net reductive TCA cycle and mild growth phenotypes with or without SDHAF2 being present. Thus, our study reveals how Complex II assembly controls a balance between dynamics of TCA cycle directionality, protection from Q-pool stress, and an ability to utilize ROS-meditated signaling to overcome acute OXPHOS dysfunction in cells reliant on mitochondrial respiration.
HostingRepository	PRIDE
AnnounceDate	2025-06-06
AnnouncementXML	Submission_2025-06-05_20:43:37.611.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-04 23:14:51	ID requested
⏵ 1	2025-06-05 20:43:38	announced

Dataset with its publication pending

submitter keyword: Mitochondria, TCA cycle, OXPHOS, SDH

David A. Stroud
contact affiliation	Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia.
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064658
     1. Label: PRIDE project
     2. Name: Complex II assembly drives metabolic adaptation to OXPHOS dysfunction