PXD040724

PXD040724 is an original dataset announced via ProteomeXchange.

Title	Mitochondria preconditioning delays aging and associated diseases in C. elegans impacting on key ferroptosis players
Description	Excessive iron accumulation or deficiency have detrimental consequences across species, leading to a variety of pathologies in humans. In the nematode Caenorhabditis elegans severe iron as well as oxygen deprivation induce developmental arrest. Instead, hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage and sub-lethal levels of iron depletion extend lifespan in C. elegans. The positive health outcomes of applying hypoxia preconditioning are obvious but have low feasible application. Here, we thus assessed the potential beneficial effects of genetic and chemical interventions acting via mild iron instead of oxygen depletion. We show that limiting iron availability through frataxin silencing or the iron chelator bipyridine, similar to hypoxia preconditioning, protect against hypoxia-, age- and proteotoxicityinduced neuromuscular deficits. Mechanistically, our data suggest that the beneficial effects elicited by frataxin silencing are at least in part mediated by counteracting ferroptosis, a form of non-apoptotic cell death specifically mediated by iron-induced lipid peroxidation. These is achieved by impacting on different key players of the ferroptosis machinery and likely via novel, gpx-independent redox systems. We thus point to ferroptosis inhibition as a novel strategy to promote healthy aging.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:01.323.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD040724
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Bernd Thiede
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-09 06:53:11	ID requested
1	2023-04-17 10:28:12	announced
⏵ 2	2023-11-14 08:45:09	announced	2023-11-14: Updated project metadata.

10.6019/PXD040724;

Schiavi A, Salveridou E, Brinkmann V, Shaik A, Menzel R, Kalyanasundaram S, Nyg, å, rd S, Nilsen H, Ventura N, impacting on key ferroptosis players. iScience, 26(4):106448(2023) [pubmed]

submitter keyword: Aging

C. elegans

fatty acids

ferroptosis

frataxin

hypoxia

iron

mitochondria

neurodegeneration

oxidoreductase

Hilde Loge Nilsen
contact affiliation	Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, Norway
contact email	h.l.nilsen@medisin.uio.no
lab head
Bernd Thiede
contact affiliation	University of Oslo
contact email	bernd.thiede@ibv.uio.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040724
     1. Label: PRIDE project
     2. Name: Mitochondria preconditioning delays aging and associated diseases in C. elegans impacting on key ferroptosis players