PXD036862

PXD036862 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics analysis of COVID-19 infected hamster lung tissue
Description	The mechanistic interplay between SARS-CoV-2 infection, inflammation, and oxygen homeostasis is not well defined. Here we show that the hypoxia-inducible factor (HIF-1α) transcriptional pathway is activated, perhaps due to a lack of oxygen or an accumulation of mitochondrial reactive oxygen species (ROS) in the lungs of adult Syrian hamsters infected with SARS-CoV-2. Prominent nuclear localization of HIF-1 and increased expression of HIF-1α target proteins, including glucose transporter 1 (Glut1), lactate dehydrogenase (LDH), and pyruvate dehydrogenase kinase-1 (PDK1), were observed in areas of lung consolidation filled with infiltrating monocytes/macrophages. Upregulation of these HIF-1α target proteins was accompanied by a rise in glycolysis as measured by extracellular acidification rate (ECAR) in lung homogenates. A concomitant marginal reduction in mitochondrial respiration was also observed as seen by a partial loss of oxygen consumption rates (OCR) in both coupled and uncoupled states of respiration in isolated mitochondrial fractions of SARS-CoV-2 infected hamster lungs. Proteomics analysis revealed specific deficits in the mitochondrial ATP synthase (Atp5a1) within complex V and in the ATP/ADP translocase (Slc25a4). The activation of HIF-1 in inflammatory macrophages may also drive proinflammatory cytokines production, complement activation, and oxidative stress in infected lungs. Together, these findings support a role for HIF-1 as a central mediator of the metabolic reprogramming, inflammation, and mitochondrial dysfunction associated with COVID-19 disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:46:33.575.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Heaven
SpeciesList	scientific name: Mesocricetus auratus (Golden hamster); NCBI TaxID: 10036;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-20 14:45:25	ID requested
1	2023-03-10 13:04:21	announced
⏵ 2	2023-11-14 07:46:37	announced	2023-11-14: Updated project metadata.

Jana S, Heaven MR, Stauft CB, Wang TT, Williams MC, D'Agnillo F, Alayash AI, -Dependent Metabolic Reprogramming, Oxidative Stress, and Bioenergetic Dysfunction in SARS-CoV-2-Infected Hamsters. Int J Mol Sci, 24(1):(2022) [pubmed]

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: COVID-19, lung tissue

Abdu Alayash
contact affiliation	Laboratory of Biochemistry and Vascular Biology Center for Biologics Evaluation and Research Food and Drug Administration
contact email	abdu.alayash@fda.hhs.gov
lab head
Michael Heaven
contact affiliation	CSO
contact email	mheaven@vulcanbiosciences.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036862
     1. Label: PRIDE project
     2. Name: Quantitative proteomics analysis of COVID-19 infected hamster lung tissue