PXD044761-1

PXD044761 is an original dataset announced via ProteomeXchange.

Title	SC-XL supercomplex protects against electron transport chain defects and alleviates ischemic heart failure
Description	According to the fluidity model, complexes of the electron transport chain (ETC) in the inner mitochondrial membrane partition between free complexes and supercomplexes. However, conclusive proof of the physiological requirement of supercomplex formation is lacking, and the mechanisms regulating their formation remain enigmatic. Here, we show that genetic perturbations affecting the biogenesis or maturation of ETC Complex III (CIII) stimulates the formation of a specialized extra-large supercomplex (SC-XL) with a predicted stoichiometry of CI2+CIII2. SC-XL formation increases mitochondrial cristae density and sustains normal ETC output despite a 70% reduction in electron flow through CIII, effectively rescuing mild to moderate CIII deficiency. Increasing the SC-XL:free CIII2 ratio significantly reduced CIII ROS production and propensity for CI ROS triggered by reverse electron transport, leading to enhanced ETC efficiency. Furthermore, higher SC-XL:free CIII2 ratio reprogrammed mitochondria towards fatty acid oxidation, enhancing endurance exercise capacity and protection against ischemic heart failure in mice. Our study reveals an unanticipated plasticity in the mammalian ETC to buttress against intrinsic perturbations via structural adaptations, and suggests that ETC reprogramming via controlled regulation of SC-XL formation is a potential therapeutic strategy for remediating diseases characterized by a decline in ETC bioenergetics and oxidative damage.
HostingRepository	PRIDE
AnnounceDate	2024-12-13
AnnouncementXML	Submission_2024-12-12_16:48:39.659.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 00:09:36	ID requested
⏵ 1	2024-12-12 16:48:40	announced

Dataset with its publication pending

submitter keyword: LC-MSMS, mouse models, metabolism,mitochondria, OXPHOS

David Stroud
contact affiliation	Department of Biochemistry and Molecular Biology, The Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, 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. PXD044761
     1. Label: PRIDE project
     2. Name: SC-XL supercomplex protects against electron transport chain defects and alleviates ischemic heart failure