PXD014573-1

PXD014573 is an original dataset announced via ProteomeXchange.

Title	1-deoxydihydroceramide causes anoxic death by impairing chaperonin-mediated protein folding
Description	Ischemic heart disease and stroke are the most common causes of death world-wide. In both pathologies anoxia, the lack of oxygen, triggers profound metabolic and cellular changes. Sphingolipids have been implicated in anoxia injury, but the pathomechanism is unknown. Here we show that injury is caused by the accumulation of the non-canonical sphingolipid, 1-deoxydihydroceramide (DoxDHCer). We found that anoxia causes an imbalance between serine and alanine resulting in a switch from normal serine-derived sphinganine biosynthesis to non-canonical alanine-derived 1-deoxysphinganine. 1-deoxysphinganine is incorporated into DoxDHCer which impairs actin folding via the cytosolic chaperonin TRiC/CCT, leading to growth arrest in yeast and increased cell death upon ischemia-reperfusion injury in worms and mouse hearts. Prevention of DoxDHCer accumulation in worms and in mouse hearts resulted in decreased anoxia-induced injury. These findings unravel key metabolic changes during oxygen deprivation and point to novel strategies to avoid tissue damage and death.
HostingRepository	PRIDE
AnnounceDate	2019-08-20
AnnouncementXML	Submission_2019-08-20_08:43:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Daniel Abegg
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	6x(13)C: 4x(15)N labeled L-arginine; 6x(13)C: 2x(15)N labeled L-lysine; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-11 07:41:36	ID requested
⏵ 1	2019-08-20 08:43:46	announced

Dataset with its publication pending

submitter keyword: C. elegans, LC-MS/MS, QExactive Plus

Alexander Adibekian
contact affiliation	Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA
contact email	AAdibeki@scripps.edu
lab head
Daniel Abegg
contact affiliation	The Scripps Research Institute
contact email	dabegg@scripps.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014573
     1. Label: PRIDE project
     2. Name: 1-deoxydihydroceramide causes anoxic death by impairing chaperonin-mediated protein folding